BrJAC-2017-V4-N15

Chemistry and the Future of Brazil April - June 2017 Volume 4 Number 15

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About Br. J. Anal. Chem.

The Brazilian Journal of Analytical Chemistry (BrJAC) is a peer-reviewed scientific journal intended for professionals and institutions acting mainly in all branches of analytical chemistry. BrJAC is an open access journal which does not charge authors an article processing fee.

Scope BrJAC is dedicated to professionals involved in science, technology and innovation projects in the area of analytical chemistry at universities, research centers and in industry.

BrJAC publishes original, unpublished scientific articles and technical notes that are peer reviewed in the double-blind way. In addition, it publishes reviews, interviews, points of view, letters, sponsor reports, and features related to analytical chemistry.

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When submitting their manuscript for publication, the authors agree that the copyright will become the property of the Brazilian Journal of Analytical Chemistry, if and when accepted for publication.

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Editorial Board Editor-in-Chief Lauro Tatsuo Kubota Full Professor / Institute of Chemistry - University of Campinas - Campinas, SP, BR Editors Cristina Maria Schuch R&I Manager / Anal. Chem. Dept. – Res. Center - Rhodia Solvay Group - Paulinia, SP, BR Elcio Cruz de Oliveira Technical Consultant / Technol. Mngmt. - Petrobras Transporte S.A. and Aggregate Professor / Post-graduate Program in Metrology - Pontifical Catholic University, Rio de Janeiro, RJ, BR Fernando Vitorino da Silva Chemistry Laboratory Manager - Nestle Quality Assurance Center - São Paulo, SP, BR Marco Aurélio Zezzi Arruda Full Professor / Institute of Chemistry - University of Campinas - Campinas, SP, BR Pedro Vitoriano Oliveira Full Professor / Institute of Chemistry - University of São Paulo - São Paulo, SP, BR Advisory Board Adriano Otávio Maldaner Criminal Expert / Forensic Chemistry Service - National Institute of Criminalistics - Brazilian Federal Police – Brasília, DF, BR Auro Atsushi Tanaka Full Professor / Dept. of Chemistry - Federal University of Maranhão, São Luís, MA, BR Carlos Roberto dos Santos Engineering and Environmental Quality Director / CETESB - Environmental Company of São Paulo State, São Paulo, SP, BR Gisela de Aragão Umbuzeiro Professor / Technology School - University of Campinas - Campinas, SP, BR Janusz Pawliszyn Professor / Department of Chemistry - University of Waterloo, Ontario, Canada Joaquim de Araújo Nóbrega Full Professor / Dept. of Chemistry - Federal University of São Carlos - São Carlos, SP, BR José Dos Santos Malta Junior Pre-formulation Lab. Manager / EMS / NC Group – Hortolandia, SP, BR Luiz Rogerio M. Silva Quality Assurance Associate Director / EISAI Lab. – São Paulo, SP, BR Márcio das Virgens Rebouças Process & Technology Manager – GranBio Research Center - Campinas, SP, BR Marcos Nogueira Eberlin Full Professor / Institute of Chemistry - University of Campinas - Campinas, SP, BR Maria das Graças Andrade Korn Full Professor / Institute of Chemistry - Federal University of Bahia - Salvador, BA, BR Renato Zanella Full Professor / Dept. of Chemistry - Federal University of Santa Maria - RS, BR Ricardo Erthal Santelli Full Professor / Analytical Chemistry - Federal University of Rio de Janeiro, RJ, BR

Br. J. Anal. Chem., 2017, 4 (15)

Contents Editorial Analytical Chemistry: an Interdisciplinary Science Interview Professor Celio Pasquini, who recently retired as Full Professor of the Institute of Chemistry at Unicamp spoke to BrJAC about his work and career Point of View Chemistry and the Future of Brazil Articles Glass and Glass-Ceramic Homogeneity Evaluation using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS)

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2-5

6-7

8-18

Preformulation Comparative Study between Two Samples of the Sorbitol used as Excipient in the Direct Compression Process

19-26

Powerful and Fast Structural Identification of Pharmaceutical Impurities using Direct Injection Mass Spectrometry and Differential Scanning Calorimetry

27-34

Technical Note On the Feasibility of Spectroscopy and Curve Resolution to Detection of Ethinylestradiol in Sewage – Preliminary studies

35-39

Sponsor Reports Combustion Ion Chromatography – Enhancing Halogen Detection Using Preconcentration Methods

40-44

Determination of Trace Elements in Naphtha using ICP OES

45-48

Feature 14th Rio Symposium presented Innovations in Atomic Spectrometry

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Releases Thermo Scientific iCAP 7000 Plus Series ICP-OES: Powerful, easy-to-use, solution for multi-element analysis

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High-Pressure Ion Chromatography System Delivers New Levels of Simplicity and Flexibility

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Centro de Pesquisas e Análises Tecnológicas: 40 Years dedicated to Quality Assurance of Fuels and Lubricants in Brazil

56-63

Events

64-64

Notices of Books

65-66

Author's Guidelines

67-69

Br. J. Anal. Chem., 2017, 4 (15), pp 1-1

Editorial

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Analytical Chemistry: an Interdisciplinary Science Pedro Vitoriano Oliveira Full Professor of the Department of Fundamental Chemistry Institute of Chemistry - University of São Paulo - São Paulo, SP, Brazil pvolivei@iq.usp.br The Analytical Chemistry is a science dedicated mainly to the development of tools and methods to answer questions related to qualitative analysis, including chemical forms, i.e., speciation, and quantitative analysis of a chemical species present in a given material. The answers to these two questions are fundamental to every field of scientific, technological, commercial and industrial knowledge. Recently, responding “where” the analyte is in the sample has also become important to understand the functionality and properties of the materials, for example, the bioavailability of elements can be highly influenced by the distribution and location in a food or environment compartment. The need to respond “where” specie or a group of chemical species is concentrated in a sample has expanding the analytical chemistry frontiers and has brought new challenges. The strategies for accessing information have been based on the combination of several techniques and professionals from different expertise. Topics such as developments in mass spectrometry combined with laser ablation to obtain spatial distribution of elements, new insights into proteomics, metallomics and metabollomics speciation analysis, sample preparation protocols and instrumentations, and new sensorial devices are some examples of challenges that require efforts of different specialists. For this reason, Analytical Chemistry is, in essence, an interdisciplinary science. It is a field of Chemistry that interfaces with Chemistry and other sciences such as Biology, Physics, Mathematics, Biochemistry, Nutrition, Pharmacy, Medicine, Engineering, among others. The proximity to other fields of science has stimulated research that focuses on the resolution of more complex issues.

Additionally, chemists with analytical knowledge have become increasingly integrated to departments and research institutes that are not necessarily associated to the Chemistry or Analytical Chemistry.

Interdisciplinary research of Analytical Chemistry has revealed new challenges and, consequently, has promoted the exchange of knowledge between Brazilians and researchers from abroad, aiming to overcome them. I believe we have not yet explored all potentialities of interdisciplinary research of Brazilian Analytical Chemistry. For this, we need to break some paradigms and believe that working in collaboration could be the best way to advance fundamental understanding or to solve problems whose solutions are beyond the scope of a single discipline or area of research practice (https://www.nsf.gov). The research funding agencies have encouraged collaborative and interdisciplinary research. For this reason, Brazilian researches groups have been working in collaboration with groups from abroad, suggesting that we are heading in the direction of advanced in the interdisciplinary analytical research.

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Br. J. Anal. Chem., 2017, 4 (15), pp 2-5

Interview

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Professor Celio Pasquini, who recently retired as Full Professor of the Institute of Chemistry at Unicamp spoke to BrJAC about his work and career Celio Pasquini Full Professor at the Institute of Chemistry, University of Campinas (Unicamp), SP, BR pasquini@iqm.unicamp.br Professor Celio Pasquini's first contact with chemistry was when he joined the Technical College of Chemistry in his city, Espirito Santo do Pinhal, located in the countryside of the state of São Paulo, Brazil. The professor left his city at the age of 17 to start his academic career at Unicamp University, when he entered the undergraduate course in Chemistry. After almost 38 years of work at the Institute of Chemistry at Unicamp he retired, keeping part of his activities at IQ-Unicamp as a Guest Researcher. Afterward he continued his studies with a Masters (1981) and a Doctorate in Chemistry (1984), both done through Unicamp. In addition, his postdoctoral degree was taken at King's College in London, England (1986).

Pasquini is the coordinator of the National Institute of Advanced Analytical Sciences and Technologies (INCTAA). He also orientates students of Scientific Initiation, Masters, Doctors and Postdoctors. The professor also participates in several chemistry meetings held in Brazil and in th the world, such as the 46 IUPAC World Chemistry Congress (IUPAC-2017), to be held July 9 to 14 in São Paulo, SP, BR. In this event, the Symposium of Analytical Chemistry will be organized by Professor Pasquini and also by Professor Joaquim Nóbrega (UFSCar). This Symposium will focus on the application of analytical sciences to everyday issues, with a confirmed presence of 14 Brazilian and foreign speakers.

Professor Celio Pasquini works in the field of Chemistry, with emphasis in Analytical Chemistry, mainly in the following subjects: flow injection analysis, monosegmented flow analysis, multivariate data analysis, near-infrared spectroscopy (NIR), laser-induced plasma emission spectroscopy (LIBS), time domain terahertz spectroscopy (THz-TD) and development of analytical instrumentation.

How was the beginning of your career? What motivated you to enter into the world of chemistry?

The factors that motivated me to enter into the world of chemistry and choose an academic career in the same area were not very different from those factors that motivated most of my high school colleagues at the time. Excellent professors of the chemistry disciplines, who knew how to show the relevance sheltered and generated by this area of knowledge and a vocation for research that was manifested at the time by curiosity and a will to understand all the concepts and phenomena that were presented to us.

Which are your research lines? What research are you currently working on?

Throughout these 38 years of work I have been active in several lines of research. The main topic of research I would say is associated with the development of analytical instrumentation, especially that focused on the development of spectrophotometric instruments. This was the research line I implemented at IQ-Unicamp shortly after my return from the postdoctoral program held at King's College in London.

However, as this main line is very eclectic, it allowed other research to be developed throughout my career.

Chemometrics is, for example, a necessary tool for the treatment of data generated by instrumentation,

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Interview especially one designed to operate in the near-infrared (NIR) spectral region. The development of this line within the research group was almost obligatory considering the results that were obtained by the development of the works in this line of instrumentation. More recently, the IQ-Unicamp research group introduced two lines of research that were unprecedented in Brazil: laser-induced plasma optical spectroscopy (LIBS) and time domain terahertz spectroscopy (THz-TD).

This body of work developed is multidisciplinary, since the development of instrumentation and methods based on instrumental techniques permeate several areas of interest such as forensic, agricultural, forestry, pharmaceutical, petrochemical and biological, among others.

Do you keep up-to-date with the progress of chemistry research? What is your opinion about the current progress of research with chemistry in Brazil?

Keeping up-to-date on the progress of chemistry, especially those related to your area of expertise is a necessary condition for any researcher. Although retired, I continue to hold interest in research and therefore am continuously informed with regards to the evolution of my research area and other related areas for which analytical instrumentation needs to be developed or improved.

In the last 10 years especially, there has certainly been a quantitative evolution of research in chemistry in Brazil. Unfortunately, the qualitative development did not accompany this evolution. Moreover, this evolutionary period was, as I observed throughout my 38-year career, only a period that ended like many previous ones, causing a discontinuity that prevents quantitative evolution from maturing toward quality.

For you, what have been the most important achievements in the analytic research field recently?

What were the landmarks? What are the latest advances and challenges in analytical chemistry?

There have been many important advances in analytical chemistry. For example, in the development of the area of materials and lasers, allowing the construction of spectrophotometers in time domain.

Consequently, spectroscopy in the THz region became feasible, with what was inaccessible by existing technologies. The lasers also allowed the development of ablation techniques, coupled to several types of detection systems, also the LIBS technique, which altered the paradigm of stand-off and direct analysis of the sample with simple or even without the need of pretreatment. The LIBS technique, for example, is embedded in the exploratory vehicle of the planet Mars, which makes elemental analysis of the rocks and soil and sends the results to be interpreted here on Earth.

The spectroscopy added a third dimension to its data by allowing the localization of chemical species in a sample through the access of hyperspectral images capable of increasing the analytical sensitivity of techniques, such as near infrared (NIR) and Raman spectroscopy. Allied to chemometrics, imaging techniques have revolutionized analytical spectroscopy. Imaging techniques allow us to locate chemical species in a sample, which answers more than just the classical questions of analytical chemistry: what and how much of a particular species is present in determined sample?

Mass spectrometry has become easier to perform in ambient conditions and is directed towards the incorporation of portable instruments. Chromatography has developed in more than one dimension allowing much more accurate and sensitive separation, identification, and quantification of species present in complex samples.

Portable and low cost instruments have been developed and demonstrated that can meet the demand for faster, direct and non-destructive analysis, reaching the point of automation without the need for specialized operators. NIR spectroscopy is an example of this.

In general, it has been observed that research in analytical chemistry has been very successful in answering the most important questions raised by society that lack reliable results. Including, from the quality, origin, and composition of food and medicines to the identification of markers for diseases that constantly afflict us, through the understanding of our environment. Within each specialty, the various analytical techniques have experienced a very rapid advance considering the time scale in science.

There are several meetings about chemistry in Brazil and the world, you participate in some of these. For you, how important are these meetings for this area and what is your opinion on the 3

Interview subject? How do you see the development of national analytical chemistry meetings in Brazil?

These events represent the opportunity to exchange knowledge and to observe advances in a more direct and personal way, with regard to the national and international researchers community. A scientific meeting always has the potential to generate collaborations, to recycle knowledge, and to update the researcher. It opens up opportunities, and in many cases demystifies the false image of researchers, instructing young researchers primarily on relevant factors, such as ethics and authentic altruism that lead to successful careers. In addition, it is a socializing and cultural event that allows peoples interaction, helping to resolve prejudices.

In Brazil, scientific meetings in the field of analytical chemistry have, in general, fulfilled their objectives.

However, its evolution has been more quantitative than qualitative, as in national science in general. We aim to have both.

Currently, you are a retired full professor of the Institute of Chemistry at the University of Campinas (Unicamp), besides, what other work do you perform? How many scientific papers have you published? Would you highlight any?

I continue to work as a Guest Researcher at IQ-Unicamp after retirement and have extended my experience in applying the knowledge accumulated in these years of work in this institution in other areas that require the use of analytical chemistry. Moreover, I have also been working as a Volunteer Professor of the Department of Soils of the Federal University of Viçosa, where I participate in a group of researchers that has a critical vision about the insertion of new analytical tools to address soil fertility and its chemical analysis, which is a complex subject.

I have acted as a consultant and instructor in several companies in which analytical problems still persist, and in which I can help transfer directly the knowledge that I accumulated in these years of work in the IQ-Unicamp.

In addition, I continue to coordinate the National Institute of Advanced Analytical Science and Technologies (INCTAA) in its phase II after the model has been well evaluated in its phase I. Which is a permanent challenge to keep more than 70 researchers from many different areas working as a network.

In my academic career I have so far published 138 scientific articles. Choosing one or two as being the most significant is very difficult. Under the scientific metric criteria, I'd have to choose those most cited by other researchers. But these are review articles that, while having the merit of spreading knowledge on a particular topic and pointing out trends and needs, do not represent contributions unheard of in the area.

As a previously unpublished contribution, I would highlight two: the one that introduced the monosegmented flow analysis technique (Pasquini, C.; Oliveira, W. A. Monosegmented System for Continuous Flow Analysis.

Spectrophotometric Determination of chromium(VI), ammonia and phosphorus. Anal. Chem., 1985, 57 (13), pp 2575-2579) and the one that introduced the spectroscopic emission technique in the near-infrared region (Pasquini, C.; Gonzaga, F. B. Near-Infrared Emission Spectrometry Based on an Acousto-Optical Tunable Filter.

Anal. Chem., 2005, 77 (4), pp 1046-1054).

Do you believe that post-graduate programs allow for the renewal of researchers in the field of analytical chemistry with quality? Is there a need that needs to be integrated?

Yes, they do allow, to the extent that researchers, who are aware of the necessity for multidisciplines, in order to not avoid purely corporatist arguments, are the ones that do the research. There is an everrecognized need to actually practice multidisciplinary science, but it always runs into programs that are not very flexible in their content regarding the subjects offered and in admission exams whose contents belong to only one subject. The real practice of being multidisciplinary is an urgent need.

What is the importance of undergraduate research programs in analytical chemistry? What are the two characteristics of these students? How do you evaluate the initiative to allow high school students access to activities related to analytical chemistry?

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Interview Scientific initiation programs are the basis for the renewal of research and researchers in any area of science, including analytical chemistry. In Brazil there are already established actions that contribute to the scientific initiation to fulfill its role in the identification of new talents and to give continuity to the development and improvement of the quality of the national research.

In my opinion, the earlier a student becomes aware of and engages in research activities, the better. It is better because they can contribute to the future of science by having their vocation awakened very early.

However if this doesn't happen, at least they will have the knowledge and insight to defend research and science, even if they don't follow a career in research. In the case of analytical chemistry, its intrinsic multidisciplinary character, and the scope of its direct action in problems related to the daily life of society, elects it as one of the most versatile areas to awaken vocations.

You are one of the Professors responsible for developing an instrument for biodiesel analysis.

How was this new technology developed? Has this technology been transferred to the private sector? Which company is responsible for its marketing?

I believe you are referring to the instrument capable of determining the oxidative stability of biodiesel and edible oils, developed on the basis of the Near Infrared Emission Technique (NIR). This work is an outcome of one of those two published works that I mentioned earlier, being well representative of the results obtained by my research group at IQ-Unicamp and scientifically relevant to analytical chemistry due to its unprecedented character.

As always, developments in the field of analytical chemistry, when motivated by the private sector, occur to solve real problems that require better ways of measuring properties or concentrations relevant to attesting the quality of products, in this case biodiesel and edible vegetable oil. This instrument has been patented, which means absolutely nothing in terms of turning it into a profitable product. No company has yet had interest in its manufacture. Therefore, the technology was not transferred to a private initiative, unfortunately something that happens very rarely in Brazil.

Could you describe how the instrument works?

The instrument works by following the chemical transformations that occur when heating a small amount of sample (a few microliters) of vegetable oil or biodiesel in the presence of air (oxidation) and generating products that emit electromagnetic radiation in the near-infrared region. The monitoring of the radiation emission intensity at previously selected wavelengths allows to determine the period in which the sample resists oxidation, called induction time, and thus determines the life time of the product. This refer to the time during which it can be stored without its properties undergoing changes, causing quality degradation and making it inappropriate for use in engines in the case of biodiesel or for ingestion in the case of edible vegetable oils. The results also guide manufacturers in adding preservatives (antioxidants) in correct amounts to preserve product quality for longer.

You have also received some awards, such as 'Unicamp Inventors Award' in more than one category. What is it like to receive this recognition? What is the importance of these awards in the development of new technologies?

All recognition for a well-done job is important. Prizes, granted for absolute merit help to keep the researcher motivated, in order to develop new projects and face the bureaucracy and other obstacles that are imposed daily to scientists in Brazil.

What would you say to a chemistry course applicant?

Welcome to the chemistry course!!! Stay, if you like to study to understand nature, to interact with it and direct it to improve our quality of life, knowing that for this you will have to face challenges and hard work.

Do not stay if you think the message that came on your cellphone during class is more important.

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Br. J. Anal. Chem., 2017, 4 (15), pp 6-7

Point of View

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Chemistry and the Future of Brazil

Luís Eduardo Duque Dutra Adjunct professor School of Chemistry Federal University of Rio de Janeiro, RJ, Brazil duquedutra@uol.com.br There will not be a shortage of natural resources, oil, and gas over the next two decades in Brazil.

According to the data of 2015, with imported oil and no gas, the country built the sixth largest chemical industry in the world and became the second offshore and biofuels producer. In view of the evident success, there is a risk of repeating the extractive cycles and not taking advantage of another opportunity, which would not be a paradox. It is the evil of abundance.

The contrast between Venice and Naples intrigued the economist Antonio Serra in the 17th century: in the north, the wealth of industrial production; in the south, agriculture and feudalism with no future. The st scarcity of lands in Venice and the opposite in Naples determined their fate [1]. For Brazil, in the 21 century, a tragedy foretold: with the largest oil province discovered in the last 20 years; the best quality iron ore; quartz mining; niobium and rare earths; the greatest biodiversity on the planet; and an immensity of arable land, the country does little to value its natural advantage.

Chemistry, biochemistry, industrial chemistry, and chemical engineering are able to do it. However, after nearly fifteen years of considerable growth of research infrastructure, training of new scientists, and the attraction of multinational research and development centers in the fields applied to the production of oil, natural gas, chemicals, and agriculture, the vitality is gone. The Brazilian economic downturn and the sudden drop in the price of oil were simultaneous and, from 2015, reduced public and private resources devoted to science and technology. If this situation continues at the same speed at which it was built, the newly created competence will be destroyed.

Research in the fields of biofuels, biogas, biorefineries, bioremediation, biofertilizers, electrochemistry, and photochemistry has been directly benefited by the conjunction of certain factors, such as: increase in raw materials prices, increasing interest in green chemistry associated with the idea of decarbonization of society, and, finally, the high oil prices until 2014. It was especially favored by the obligations to provide support to technological development of oil and electricity concession agreements. In 2012, the Institute for Applied Economic Research (Ipea) estimated that the revenue of national research infrastructure had reached 1.4 billion reais (Brazilian currency), which was a record, and Petrobras accounted for 23% of the total. In the same year, financing amounted to 1.6 billion reais, of which 304 million reais were for oil and gas, and 205 million reais for renewable energy [2].

The infrastructure is new and widespread in the universities and research institutes. There are some centers of excellence; however, this infrastructure has neither the critical size nor even the essential articulation to survive. In the renewable energy sector, among a hundred laboratories listed, eleven are researching the use of biomass. With the exception of the Brazilian Bioethanol Science and Technology Laboratory (CTBE), which is public and was opened in 2010, and the Sugarcane Research Center (CTC), which is private and was the former Copersucar research unit, none of them had a revenue greater than 20 million reais in 2012 (the average was only 2 million reais). With this limited budget, it is difficult for small units with no coordination to obtain results.

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Point of View With the barrel of oil at 100 U.S. dollars, the huge challenge becomes a Herculean task with the price dropping to 50 U.S. dollars. To this fact, it should be added the greatest economic downturn in the country and the reversal of the raw materials and agricultural products cycle, the latter being initiated in 2012. The expenditure on research is always the first to be cut. Expenditures on biofuels research will not reach 100 million reais in 2017, and not even the half for the chemical industry. According to the National Agency of Petroleum, Natural Gas and Biofuels, the obligations for research and development in the oil and gas sector reached 1.4 billion reais in 2014 [3]. In 2017, there would be a total 900 million reais if the complete expenditure is performed, which will certainly not occur. Even with the fall, the comparison reveals the disproportion of the means.

The only good news is that, whatever the fate, there will not be a shortage of laboratories and competence. The current achievements, however, do not allow biofuels, bioderivatives, biogas, biofertilizers, and everything else to compete with oil and gas derivatives. Up to now, waiting for the second generation of biorefineries, only bioelectricity generated by biomass burning has found space.

Definitely, this is not a major breakthrough. To go beyond, five to ten years of research will be required.

The assets are installed, the university courses have multiplied, and the professionals have been trained.

In spite of the absence of public policies and in view of the economic crisis and shortage of means, science cannot refrain from the future of the country.

1. Quoted by Reinert, E. S. Como os países ricos ficaram ricos… e por que os países pobres continuam pobres. Contraponto Editora, Rio de Janeiro, BR, 2016, p 48.

2. De Negri, F.; Squeff, F.de H. (organizers). Sistemas setoriais de inovação e infraestrutura de pesquisa no Brasil. Instituto de Pesquisa Econômica Aplicada – IPEA, Brasília, BR, 2016.

3. http://www.anp.gov.br/wwwanp/pesquisa-desenvolvimento-e-inovacao/investimentos-em-p-d-i/recursos st -financeiros-das-clausulas-de-investimentos-em-p-d-i (accessed on 31 May 2017).

Luís Eduardo Duque Dutra has a Ph.D. in economics from Paris-Nord University, and specialization in Intellectual Property from WIPO Academy (World Intellectual Property Organization) and the University of Turin. He is adjunct professor at the School of Chemistry of the Federal University of Rio de Janeiro, Brazil.

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Br. J. Anal. Chem., 2017, 4 (15), pp 8-18

Article

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Glass and glass-ceramic homogeneity evaluation using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) 1

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Jeyne Pricylla Castro , Leonardo Sant'Ana Gallo , Edgar Dutra Zanotto , Edenir Rodrigues Pereira-Filho1* 1

Group for Applied Instrumental Analysis (GAIA), Department of Chemistry, Federal University of São Carlos, São Carlos, SP, P.O. Box 676, Zip Code 13565-905, Brazil 2 Vitreous Materials Laboratory, LaMaV, Materials Engineering Department, DEMa, Federal University of São Carlos, São Carlos, SP, Zip Code 13565-905, Brazil

Graphical Abstract

Direct homogeneity analysis of high performance glass and glass-ceramic using laser ablation ICP-MS (LA-ICP-MS)

Laser ablation hyphenated with inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to evaluate the homogeneity of high performance glass and glass-ceramic samples. Signal 10 26 27 47 90 121 profiles of B, Mg, Al, Ti, Zr and Sb were monitored, and solid samples were analyzed directly without sample preparation.

A fractional factorial design was used to evaluate the influence of 6 parameters. A matrix with 5 rows and 5 columns (total of 25 points) was analyzed for 6 samples (3 glasses and 3 glassceramics). Fifty pulses were conducted at each point to observe the surface, and 50 additional pulses were later conducted at the same positions to observe the bulk.

The analyzed samples presented homogeneous surface and bulk profiles with respect to the main oxide elements (Al and Mg) and nucleating agents (Ti and Zr). Relative standard deviations (RSDs) for the monitored elements varied from 3.2 to 23.2%. When the glasses were compared with the glass-ceramics, 10 significant differences were observed only for B. Al and B presented high signals at the bottom of the samples (top of the melting crucible). In contrast, Zr and Ti presented homogeneous profiles throughout the samples.

Keywords: Ballistic glass, laser ablation, ICP-MS, homogeneity.

INTRODUCTION There are different definitions of glass in the scientific literature; one of the most widely accepted was proposed by Zarzycki: “glass is a non-crystalline solid that presents glass transition” [1]. This definition considers not only common oxide glasses but also organic and metallic compounds. Glasses do not present long range order in their structural units, the coordination polyhedral [2]. The most common way to produce a glass is by rapidly cooling a melt to room temperature, avoiding crystallization [3]. Glasses are thermodynamically less stable than the corresponding crystalline structure, and at room temperature, crystallization is prevented by the kinetic barrier to the diffusion of its compounds. Energy is provided by heating, and a glass can crystallize, lowering the thermodynamic energy of the structure. The crystallization process starts with nucleation and can be divided on homogeneous and heterogeneous processes [1]. In the former case, the nuclei have the same probability of be formed on the surface or in the bulk of the glass.

In the latter, nucleation occurs at preferential sites, such as surfaces, internal flaws like cracks, bubbles, and undissolved particles in the bulk. *erpf@ufscar.br

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Glass and glass-ceramic homogeneity evaluation using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)

Article

In the case of oxide glasses, most compositions do not present detectable internal homogeneous nucleation. To promote it, some oxides, called nucleating agents, are added to the composition, promoting bulk nucleation. Some glass systems, such as Li2O-SiO2, can present homogeneous bulk nucleation without the addition of nucleating agents. In contrast, the MgO-Al2O3-SiO2 glass system requires nucleating agents.

To evaluate the homogeneity of the glass and glass-ceramic samples, a sampling technique that permits direct solid analysis with high analytical frequency was employed. Adequate microstructure homogeneity is related to the possibility to obtain reproducible properties, such as nucleation and crystallization rate and also the crystalline phases present after crystallization. To verify homogeneity, laser ablation (LA) is a natural choice because it combines the properties mentioned above and employs a short-pulsed, highpower laser beam focused onto the sample surface, converting a finite volume of the solid sample into its particles constituents. These particles can be analyzed by atomic/ionic emission in the induced plasma (LIBS, laser-induced breakdown spectroscopy) [4] or by other techniques, such as inductively coupled plasma-mass spectrometry (ICP-MS), where the particle is transported and the analytes are atomized/ ionized and sequentially measured [5].

Inductively coupled plasma-mass spectrometry hyphenated with laser ablation (LA-ICP-MS) presents several advantages as a powerful technique that combines the high sensitivity and multielemental capability of ICP-MS with the good spatial resolution and direct analysis of solid samples by laser radiation [6]. This combination has the potential for non-destructive determination of a large number of elements with low limits of detection and minimal or no sample preparation procedures. However, there are limitations, such as interference, calibration difficulties and elemental fractionation [7].

Several applications using LA-ICP-MS have been described in the literature for various samples, such as environmental, [6,8-10] forensic, [11-13] biological, [14] waste materials [15] and materials science [16].

In the specific case of glasses the majority of applications are devoted to forensic analysis, [17] historical purposes, [18] semi-quantitative analysis [19] and defects characterization [20].

The aim of this study was to verify the homogeneity of glass and glass-ceramic samples by observing the chemical profiles of Ti and Zr (nucleating agents) and some of the constituents (Al, B, Mg, and Sb).

Laser ablation-ICP-MS was performed without any sample pretreatment.

MATERIAL AND METHODS Samples This study analyzed glass and glass-ceramic samples prepared by the authors at the Vitreous Material Laboratory (Materials Engineering Department, Federal University of São Carlos). The components of the samples were SiO2, MgO, Al2O3, B2O3, Sb2O3, ZrO2 and TiO2. Zr and Ti oxides homogeneities were responsible for the high material performance. The proposed glass formulation is from the MgO-Al2O3-SiO2 system. Glasses within this system can crystalize, after proper heat treatments, hard phases like spinel (MgO.Al2O3; HV = 15.4 GPa), sapphirine (4MgO.5Al2O3.2SiO2; HV = 13.3 GPa) and cordierite (2MgO.2Al2 O3.5SiO2 - similar HV to sapphirine). HV is a unit of hardness derived by a test named Vickers Hardness test, one of the most common on engineering. Glass-ceramics having these phases can be used, for example, as materials to block high kinetic energy blasts (ballistic glass-ceramics) or even be used as smartphone's and tablet's screens. The major constituent is SiO2, since this glass is a silicate. Together with MgO and Al2O3, these oxides (B2O3; Sb2O3; ZrO2 and TiO2) are responsible for the crystallization of the desired crystal phases. TiO2 and ZrO2 are the nucleating agents. This glass does not crystallize on the bulk without the aid of such oxides. B2O3 is a glass former and Sb2O3 a fining agent. Due to the viscosity, the obtaining of a homogeneous glass is a challenging task.

A crystalline material obtained by the process of crystallization of a glass is called a glass-ceramic. The glass-ceramic can present stoichiometric crystallization (when the crystal phase has the same stoichiometry of the parent glass), or non-stoichiometric (when the crystal phase and the parent glass have different

9

Castro, J.P.; Gallo, L.S.; Zanotto, E.D.; Pereira-Filho E.R.

Article stoichiometry). The analyzed glass in this study is non-stoichiometric. After the melting of the constituents, six samples were prepared. Using sandpaper, all the samples had two opposite faces made parallel.

Three of these glass samples were crystallized on a double-stage heat treatment, i. e., the glass was subjected to heat treatments at two different temperatures: the glass sample is heated above the glass transition temperature (Tg = 773 °C and Tnucleation = 805 °C) for a period of time to promote nucleation; the temperature is then increased to promote crystal growth (Tgrowth = 960 °C). The crystallization promotes changes on an atomic scale. The glass that originally presented no long-range order, now has crystalline phases, i. e, oriented structural units. This structural difference promotes changes on several properties, like optical, mechanical, chemical among others.

In this work, the glass composition uses TiO2 (4.36% w/w) and ZrO2 (6.35% w/w) as nucleating agents.

Several compounds are added: B2O5 as a glass former oxide, Sb2O5 to reduce the viscosity and to assist the elimination of bubbles, and the main oxides (MgO, Al2O3 and SiO2) to promote the crystallization of the desired crystal phases.

These samples were divided into three sections: top, middle and bottom, which refer to the reverse position of the glass melt in the crucible. A top sample means that the glass melt was on the bottom of the melting crucible, and a bottom sample refers to a glass melt that was on top of the melting crucible. Six sub-samples were used (3 glass samples and 3 glass-ceramic samples). In this case, it is important to qualitatively evaluate the elements present, to see if at different parts (bottom, middle and top) of the glass we would have the same signal of the original elements (Al, Mg, B, Sb, Ti and Zr). This is important when one thinks about the product performance. The original glass, prior to the crystallization, must be homogeneous to generate a homogeneous glass-ceramic. Finally, since Si is, by far, the major constituent (approximately 50% of total mass), it was not necessary to verify its homogeneity.

Instrumentation LA experiments were conducted using an LSX-213 G2+ laser system (Teledyne CETAC Technologies, Omaha, NE, USA) coupled to an iCAP Q ICP-MS instrument (Thermo Fisher Scientific, USA). Table I shows the parameters used for both instruments.

Table I. Instrumental parameters used in the LA-ICP-MS. Instrumental parameters for LA Analyzed area pattern for each sample -1 Scan rate (µm s )

Matrix with 5 rows and 5 columns (25 points) and 50 pulses per point 40

Instrumental parameters for ICP-MS Radio frequency (RF) generator (MHz)

27

RF applied power (kW)

1.55 -1

*Spot size (µm)

200

Argon gas flow rate (L min )

*Repetition frequency (Hz)

10

Auxiliary gas flow rate (L min )

*Laser energy (mJ)

4.7

Nebulizer gas flow rate (L min )

1.18

Fluence (J cm )

15

Sampling depth (mm)

5.0

Irradiance -2 (GW cm )

3.0

Integration time (s)

3.0

*He flow rate 1 -1 (mL min )

350

Sampling cone (mm)

Nickel 0.8

He flow rate 2 -1 (mL min )

200

Skimmer cone (mm)

Nickel 1.2

*Additional Ar flow -1 rate (mL min )

250

Nebulizer

-2

14.0 -1

0.8

-1

Glass concentric (MicroMist)

Spray chamber -

Mass/charge ratios monitored: B, 121 and Sb

*Variables evaluated using a fractional factorial design 10

Cyclonic 10

26

Mg,

27

Al,

47

Ti,

90

Zr,

Glass and glass-ceramic homogeneity evaluation using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)

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Optimization of the LA system Some parameters of the LA were studied by applying a 26-2 fractional factorial design with central point.

In a full factorial design with 4 variables, for example, the variables are studied in 2 levels and a total of 4 16 (2 ) experiments are performed. As can be noted the number of experiment increase exponentially with the number of variables. Using this type of experiment is possible to calculate individual variables effects and interactions between 2 variables and among 3 and 4 variables. In general, individual effects are higher than interaction effects. In an experimental design with 6 variables and 2 levels a total of 64 (26) experiments can be done. This number of experiments is very huge and sometimes unnecessary in order to identify the most appropriate working conditions.

Among the parameters described in Table I, six variables were investigated: (v1) He flow rate 1 (mL min-1), (v2) Ar flow rate (mL min-1), (v3) spot size (μm), (v4) repetition frequency (Hz), (v5) laser energy (mJ) and (v6) ablation speed (μm s-1), which were studied at three levels (-1, 0 and +1), as shown in Table II. The He flow rate 1, e.g., was tested at 350 (coded as -1), 525 (coded as 0, central point) and -1 700 mL min (coded as 1). In the Table I, there are two He flow rate. The He flow rate 1 is responsible for transporting the ablated sample particles and He flow rate 2 is responsible for cleaning the ablation cell and maintaining an inert atmosphere. In this case, a fractional factorial design can be performed. In 6-2 the specific case of this study, a 2 with 6 variables was prepared, but only 16 experiments were done.

In Table II the variable 5 (laser energy) was build multiplying variables 1, 2, 3 e 4. Variable 6 (ablation speed) was obtained after multiplying variables 1, 2 and 3. This implies that individual effects are mixed (confounded) with effects of fourth and fifth order. As interaction effects are probably lower than individual effects, using a fractional factorial design we can obtain an estimative of individual effects, identify the most important variables and the most appropriate instrumental condition.

Table II. Fractional factorial design (26-2) for optimization of the LA parameters

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Castro, J.P.; Gallo, L.S.; Zanotto, E.D.; Pereira-Filho E.R.

Article A glass standard reference material (NIST 710a) was used to select the most appropriate operational conditions. In all experiments, a scan line of approximately 3 mm was used. Thus, the ablation speed was used only in the optimization part. The elements described in Table I were monitored with the goal of selecting the condition with the maximum intensity (highest sensitivity). Signal area was calculated with the signal profile obtained and the six responses were merged in only one response using desirability function [21]. In this case, the lowest and the highest signals area were converted to 0 and to 1, respectively [22]. Later, the geometric mean (global desirability, Dg) was calculated in order to obtain a single response that combines the 6 evaluated elements.

Homogeneity of the samples To verify the homogeneity of the samples, 25 points were ablated using a matrix pattern with 5 rows and 5 columns (see Table I). The points were separated by 200 μm and covered an area of approximately 3 mm2 (1.8 x 1.8 mm). Analyses were divided into two steps: (1) 50 pulses were performed at each point (25 points) and then (2) additional 50 pulses were performed at the same positions. The goal was to observe the homogeneity at the surface (first 50 pulses) and in the bulk (second 50 pulses) of the samples. The ablated area characteristics were evaluated using an optical microscope (Nikon, model Eclipse LV 100N Polarizing) equipped with a digital camera. This procedure was performed for glass and glass-ceramic samples in bottom, middle and top parts.

RESULTS AND DISCUSSION Laser ablation optimization In the optimization process, the most important variables (strongest effects) were v2 and v3. Variable 2 (Ar flow rate) had a negative effect, and high analyte signals were obtained when this variable was at its -1 low level (-1, 250 mL min ). Variable 3 (spot size) had positive effects, and intense signals were observed when a larger area was ablated (+1, 200 μm). Figure 1 shows a pictorial description of the effects calculated. In the case of variable 2 (Ar flow rate) the average global desirability (Dg) in the highest (+1) and lowest (-1) levels were 0.017 and 0.256, respectively. In this case, the variable 2 effect is 0.017-0.256 = -0.240. It means that when the variable 2 is used in the higher level (+1, 500 mL min-1) the signal for all -1 six elements decrease. Finally, is better to use variable 2 in the lowest level (-1, 250 mL min ). In Figure 1 is observed that the arrow is proportional to the effect. Variables 2 and 3 presented the biggest arrows.

Figure 1: Pictorial description of the effects calculated in the 26-2 fractional design. The size of the arrow is proportional to the effect.

The other variables had negligible effects in the studied range when compared with variables 2 and 3 (presented smaller arrows). The operational conditions selected for further experiments were those 12

Glass and glass-ceramic homogeneity evaluation using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)

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described in experiment 4 (Table II): v1 = 350 mL min-1, v2 = 250 mL min-1, v3 = 200 μm, v4 = 10 Hz, v5 = -1 4.7 mJ and v6 = 60 μm s . This condition presented a Dg of 1.

Tests of homogeneity Figure 2 shows images of the ablated area (5 x 5 points) and ablated points. The crater diameter is approximately 200 µm. The depth of the craters was estimated to be approximately 20 µm. Each set of 50 pulses corresponds to 10 µm. The depth of the craters was estimated by focusing on the surface of the sample and then the internal part of the crater. The optical microscope was able to estimate the difference in µm between the two focusing stages. Some craters presented an irregular shape probably due to the irregular surface of the samples that compromise the focusing step during ablation process or the laser was not able to ablate the whole area. Unfortunately, it was not possible to obtain a perfect plain surface due to the natural characteristics of the material (high hardness).

Figure 2: Characterization of the ablated area and points (matrix with 5 rows and 5 columns).

Figure 3 shows the signal profile for aluminum (27Al) in the glass (Figure 3a) and glass-ceramic (Figure 3b) samples, indicating homogeneity in the analyzed samples: bottom, middle and top. The same tendency 26 was observed for Mg (present in the oxide form). The analytical frequency was approximately 4 min per sample, and the scales of the y axis in the figure were the same for comparison purposes.

Figure 3: Aluminum signal profile (27Al) for (a) glass and (b) glass-ceramic samples.

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Castro, J.P.; Gallo, L.S.; Zanotto, E.D.; Pereira-Filho E.R.

Article In addition, a reduction in the signal intensity was observed in the glass-ceramic samples, and the signal was greater for the bottom samples. The same trend was observed for B (10B). In contrast, Sb presented a homogeneous profile, but the signal in the glass-ceramic bottom sample was lower than in the middle and top glass samples.

47

The nucleating agents of the glass were Ti and Zr. Figure 4 shows the signal profile for Ti ( Ti), which presented a homogeneity among the points in the two analyzed samples (glass and glass-ceramic) and its fragments (bottom, middle and top). The glass-ceramic presented a lower intensity than the glass, as observed for the other analytes.

Figure 4: Titanium signal profile (47Ti) for (a) glass and (b) glass-ceramic samples.

Figure 5 shows 3D graphs with the entire analyzed area (matrix of 5 rows and 5 columns) for Zr (90Zr) with 50 and 100 pulses for two samples. For glass, the bottom presented a lower intensity than the middle and top, which showed an intensity 1.4 times higher, as it would be expected, since ZrO2 has a high density compared to the other constituents and, due to gravity, would go to the bottom of the crucible. For glass ceramic (Figure 5c and Figure 5d), the bottom, middle and top, presented a similar distribution. The same tendency was observed for 47Ti comparing the glass and glass-ceramic, the intensity of glass was higher.

No remarkable differences were observed between the signal profiles of the first 50 pulses and the second set of 50 pulses. Thus, a homogeneity was observed throughout the analyzed area of the samples studied.

14

Figure 5: Zirconium signal distribution (90Zr) for (a) glass with 50 pulses, (b) glass with 100 pulses, (c) glass-ceramic with 50 pulses and (d) glass-ceramic with 100 pulses. (For interpretation of the references to color in this ďŹ gure legend, the reader is referred to the web version of this article.)

The RSD values for each point of the matrix (25 points, 5 rows and 5 columns) was made for 121Sb, 27Al, 90 10 47 Zr, B and Ti for two samples (bottom, middle and top) with 50 and 100 pulses, as observed in the Figure 6. In the case of glass, the values varied from 3.2 (in the point 13 for top of 90Zr with 50 pulses) to 121 23.2 (in the point 15 for bottom of Sb with 50 pulses). In the case of glass-ceramic, the values varied 27 from 3.7 (in the point 13 for top of Al with 100 pulses) to 16.1 (in the point 23 for top of 121Sb with 50 pulses). It was not observed a large variability between RSD values in the analyzed area (matrix of 5 rows and 5 columns), observed in Figure 6. This is a positive factor, showing a homogeneity of the samples.

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Glass and glass-ceramic homogeneity evaluation using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)

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Figure 6: RSD values for 121Sb, 27Al, 90Zr, 10B and 47Ti for bottom, middle and top. (a) Glass with 50 pulses, (b) glass with 100 pulses, (c) glass-ceramic with 50 pulses and (d) glass-ceramic with 100 pulses.

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Castro, J.P.; Gallo, L.S.; Zanotto, E.D.; Pereira-Filho E.R.

Article Analysis of variance (ANOVA) was performed to verify the homogeneity of the samples with respect to both the analyte peak area and height. In this step, we organized a matrix X with two columns (intercept or b0 and slope or b1). The intercept was a column with ones (1) and the b1 was the ablated positions from 1 to 25. The vector y was the averaged signal (for signal height) or sum (for signal are) obtained in each 25 points. Later, we calculated the coefficients (b) using: t

-1

t

b = (X X) X y For the majority of cases, only the constant (b0) was significant. The linear coefficient (b1) was lower than the confidence interval with 95% of confidence level in a few cases and the regression was not 2 27 significant (R values lower than 0.5). Table III shows an Anova table for Al. As can be observed from the Anova table described the model is not significant, with F and R2 values very small.

Table III. Anova table for 27Al homogeneity evaluation.

Degree of Mean of Test F freedom square

Sum of Square Regression 9.69e+16

1

9.69e+16

Residue

1.38e+18

23

6.01e+16

Total

1.48e+18

24

6.16e+16

2

R

1.612. Tabulated F with 1 and 23 degree of freedom and 95% of confidence level = 4.28

0.065

The model obtained was: 27

Al area = (3.82e+9 ± 2.10e+8) + (8.63e+6 ± 1.41e+7)x

As can be noted the coefficient b1 (8.63e+6) is lower than its confidence interval (1.41e+7). Finally, only the intercept (b0 = 3.82e+9) is statistically valid at a 95% of confidence level.

A paired t test for multiple samples [23] was performed to compare the signals of the glass and glass10 ceramic for the studied elements, and a significant difference was observed only for B at the 95% confidence level.

CONCLUSION The analyses performed on the glass and glass-ceramic samples showed that the constituents are homogeneously distributed throughout the glass and the crystallization process does not promote irregular distribution for the majority of the elements. Aluminum and boron presented high analytical signals in the bottom samples. This was expected since they are lighter elements than the other constituents and may rest on the top of the melting crucible (bottom of the sample). In contrast, antimony is heavy and stayed on the bottom of the melting crucible, resting on top of the glass and glass-ceramic samples. Zirconium and Ti, which are nucleating agents, were used in small concentrations during the samples preparation due to the oxide solubility limits in silicate glasses. In addition, they have high melting points compared to the other elements. We expected high signals at the bottom of the crucible (top of the sample) because these elements were the last to melt. Surprisingly, these elements were in general uniformly distributed throughout the sample and the signal intensity ratio between bottom (top of the sample) and top (bottom of the samples) was in the order of 1.4.

The proposed procedure is an important tool in the field of glass science for the analysis of high performance glass homogeneity and for the preparation of glass.

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Glass and glass-ceramic homogeneity evaluation using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)

Article

ACKNOWLEDGEMENTS This study was supported by the São Paulo Research Foundation (FAPESP), 2014/22408-4 (MSc) and 2016/17221-8 (PhD) grants to JPC, a 2013/00457-0 PhD grant to LSG and by 2013/07793-6 (CEPID) and the “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq, 401074/2014-5 and 305637/2015-0). The authors are grateful to Nova Analítica, Thermo Scientific and CETAC for the instrument loans.

Manuscript received July 5, 2016; revised manuscript received Aug. 22, 2016; manuscript withdrawn by the authors Sept. 12, 2016; second submission: May 31, 2017; manuscript accepted June 7, 2017.

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2. Chiang, Y.-M.; Birnie, D.P.; Kingery, W.D. Physical Ceramics: Principles for ceramic science and engineering, John Wiley, New York, 1997, p 522.

3. Fokin, V.M.; Zanotto, E.D.; Yuritsyn, N.S.; Schmelzer, J.W.P. J. Non-Cryst. Solids, 2006, 352, pp 2681-2714.

4. Pasquini, C.; Cortez, J.; Silva, L.M.C.; Gonzaga, F.B. J. Braz. Chem. Soc., 2007, 18, pp 463-512.

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6. Nunes, M.A.G.; Voss, M.; Corazza, G.; Flores, E.M.M.; Dressler, V.L. Anal. Chim. Acta, 2016, 905, pp 51-57.

7. Mokgalaka, N.S.; Gardea-Torresdey, J.L. Appl. Spectrosc. Rev., 2006, 41, pp 131-150.

8. Arroyo, L.; Trejos, T.; Gardinali, P.R.; Almirall, J.R. Spectrochim. Acta B, 2009, 64, pp 16-25.

9. Yi-Ling, L.; Chao-Chiang, C.; Shiuh-Jen, J. Spectrochim. Acta B, 2003, 58, pp 523-530.

10. Chirinos, J.R.; Oropeza, D.D.; Gonzalez, J.J.; Hou, H.; Morey, M.; Zorba, V.; Russo, R.E. J. Anal. At. Spectrom., 2014, 29, pp 1292-1298.

11. Neufeld, L.; Spectroscopy, 2005, 20 (available at http://www.spectroscopyonline.com/applicationlaser-ablation-icp-ms-analysis-forensic-glass-samples).

12. Wang, X.; Motto-Ros, V.; Panczer, G.; De Ligny, D.; Yu, J.; Benoit, J.M.; Dussossoy, J.L.; Peuget, S. Spectrochim. Acta B, 2013, 87, pp 139-146.

13. Karasev, A.V.; Inoue, R. Mater. T., 2009, 50, pp 341-348.

14. Hanc, A.; Olszewska, A.; Baralkiewicz, D. Microchem. J. 2013, 110, pp 61-69.

15. Coedo, A.G.; Padilla, I.; Dorado, M.T. Talanta, 2005, 67, pp 136-143.

16. LaHaye, N.L.; Kurian, J.; Diwakar, P.K.; Alff, L.; Harilal, S.S. Scientific reports, 2015, DOI: 10.1038/srep13121.

17. Trejos, T.; Koons, R.; Weis, P.; Becker, S.; Berman, T.; Dalpe, C.; Duecking, M.; Buscaglia, J.; Eckert-Lumsdon, T.; Ernst, T.; Hanlon, C.; Heydon, A.; Mooney, K.; Nelson, R.; Olsson, K.; Schenk, E.; Palenik, C.; Pollock, E.C.; Rudell, D.; Ryland, S.; Tarifa, A.; Valadez, M.; Van Es, A.; Zdanowicz, V.; Almirall, J. J. Anal. At. Spectrom., 2013, 28, pp 1270-1282.

18. Wagner, B.; Nowak, A.; Bulska, E.; Kunicki-Goldfinger, J.; Schalm, O.; Janssens, K. Microchim. Acta, 2008, 162, pp 415-424.

19. Imbert, J.L.; Telouk, P. Microchim. Acta, 1993, 110, pp 151-160.

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Br. J. Anal. Chem., 2017, 4 (15), pp 19-26

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Preformulation Comparative Study between Two Samples of Sorbitol used as Excipient in the Direct Compression Process *

Renan Marcel Bonilha Dezena , José dos Santos Malta Junior EMS Indústria Farmacêutica, Hortolândia, SP, Brazil The behavior of pharmaceutical formulations is dependent on the production process, interaction between the excipients and the active pharmaceutical ingredient (API). Therefore it is necessary to carry out a preformulation study for a better understanding of the physical and chemical characteristics that directly affect the stability of the finished product. A preformulation study was performed on the sorbitol present in raw materials from two different manufacturers through the determination of particle size distribution (PSD) by laser diffraction, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Analysis by FTIR, XRD and DSC showed that there were differences in the polymorphic forms of sorbitol present in the raw materials. The results obtained in the polymorphism tests showed that the first sample of sorbitol raw material contained a stable polymorphic form (gamma) while in the second sample there was a mixture of polymorphic forms (a stable polymorphic form called gamma and a metastable polymorphic form, epsilon). This suggested the need for quality control regarding the type of polymorph to be used in the production of sorbitol formulations to ensure greater therapeutic efficacy.

Keywords — Preformulation, polymorphism, excipients, X-ray diffraction, differential scanning calorimetry.

INTRODUCTION A complete understanding of the physicochemical properties of a drug substance is the first step in the pharmaceutical study defined as preformulation. Chemical and physical properties are intrinsic to each drug; therefore, solid state characterization will be helpful as an initial analysis. A range of properties can be characterized: organoleptic properties, bulk characteristics (particle size distribution and shape), powder flow properties (such as angle of repose), density, compressibility, crystallinity, polymorphism, hygroscopicity, solubility, ionization constant, partition coefficient, dissolution, drug-excipient compatibility studies and stability [1,2].

Preformulation is useful for a better selection of the drug candidate, formulation components, active pharmaceutical ingredient (API), drug product manufacturing processes, the most appropriate container closure system, development of analytical methods, the synthetic route to the API, the rational development of dosage forms and toxicological strategy. Preformulation studies are important in scientific research because they support the control of the supply of raw materials and preserve resources in drug research and development, thus improving product quality and providing strategies for the formulation process [3-7]. In addition, advances in techniques for characterization of solid dosage forms leads to prediction of physical and chemical stability as a function of preparation and processing.

Polymorphism and pseudo polymorphism are solid state properties that can affect solubility, intrinsic dissolution rates, bioavailability and formulation stability, which are important to the successful development of pharmaceutical products [8]. Fundamental questions include the investigation of polymorphism – the ability of a compound to exist in more than one crystalline form – and careful evaluation of the solid form for development [9].

The difference in entropy associated with physical forms (amorphous, different polymorphs or solvates) leads to measurable differences in physical properties [9]. Two polymorphic forms of sorbitol are known and defined as the (stable) gamma form and the (metastable) epsilon form [10-11]. *renan_marcel@hotmail.com 19

Article

Preformulation Comparative Study between Two Samples of Sorbitol used as Excipient in the Direct Compression Process

Sorbitol (C6H14O6), also referred to as D-glucitol, is widely marketed and disseminated worldwide and has different applications in the food, confectionery and pharmaceutical industries. It is used as an agent in the production of vitamin C and other pharmaceutical products. When exposed to the milling/micronization process many solids undergo direct transformations from a crystalline to a glassy amorphous state, while other crystals convert into a less stable polymorphic form. The structural changes upon milling/micronization increase the number of crystal defects and shear deformations, induced by the mechanical stress. Studies have found that amorphizations are generally observed when milling/micronization is performed below the glass transition temperature of the compound, while polymorphic transformations mainly occur during milling/micronization above the glass transition temperature. This indicates that the thermodynamic principles involved in the amorphic/polymorphic transformation are according to the physics of nonequilibrium phenomena [12-13].

Besides the conversion of polymorphic forms that may occur during the drug manufacturing process, a better evaluation of the raw materials is necessary, since the same molecular compound may already be present initially as a mixture of polymorphic forms, depending on the synthetic route used by the manufacturer. Therefore, prior to the manipulation of the raw material in formulations in the pharmaceutical industry it is essential to characterize its polymorphic form and to enable a better understanding of the predominant factors that have a direct impact on product quality [14].

The study of polymorphism has now become relevant not only in relation to the active pharmaceutical ingredients, but also in relation to the excipients present in the formulation, because they are usually the principal fraction of a pharmaceutical formulation. It is well known that the behavior of the pharmaceutical form is dependent on the production process, the interaction between the excipients, and the impact of the same on the active ingredient and the pharmaceutical form. Excipients previously regarded as simple administration and stabilizing substances of the preparation are now considered to be essential constituents that ensure the performance and safety of the medicinal product and the attainment of the therapeutic effect, and should therefore be the subject of important considerations during the preformulation phase [15-16].

It was possible to perform the physical chemical characterization of sorbitol samples through the determination of particle size distribution (PSD) by laser diffraction, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) [17].

In this work a comparative preformulation study of two samples of sorbitol raw materials from different manufacturers and their possible impact on the direct compression process was carried out, because sorbitol exhibits a polymorphic transformation.

MATERIAL AND METHODS Samples The two samples of sorbitol raw material for the direct compression process were obtained from different manufacturers.

Particle size analyses were conducted under the conditions below: · Analysis module: Dry Powder System (DPS) · Obscuration: 4% · Target vacuum: 19 inH2O · Sample weight: 3.0 g Analyses in the infrared region were obtained under the conditions below: · Germanium crystal with ATR accessory · Background: 32 scan · Spectrum obtained: 128 scan · Resolution: 4 cm-1 Thermal analyses were conducted under the conditions below: · Initial temperature: 25 ºC 20

Dezena, R.M.B.; Malta Junior, J.S.

Article · · · ·

-1

Heating rate: 10 °C min Final temperature: 350 ºC Nitrogen flow: 80 mL min-1 Analysis container: 40 µl aluminum (Al)

X-ray diffraction analyses were conducted under the conditions below: · · · · · · ·

2θ: 2 to 40º φ: 223.2º Variable rotatic [1/min]: 15.0 Voltage: 30 kV Current: 10 mA Tube: Cu tube with 1.54184 Å Detector: Lynxeye

RESULTS AND DISCUSSION Determining which critical attributes interfere directly with the quality of pharmaceutical products is crucial in ensuring efficacy and safety, particularly by establishing appropriate limits, range and distribution.

Among these critical attributes we can specifically highlight a very important property of the solid dosage forms: particle size distribution [18]. Most of the methods used in the manufacture of API particles involve crystallization processes that generally lead to formation of heterogeneous particle growth, resulting in a variability of particle size [19].

The process known as direct compression represents an interesting option because it allows a reduction in the number of steps and in production time. This process requires high powder flowability and compactability of the active pharmaceutical ingredient and excipients to ensure the consistency of each tablet, so it is necessary to analyze and control the particle size distribution of the formulation components since it directly affects the compaction performance [20].

The samples showed practically the same results of particle size distribution when evaluating the parameters d10, d50 e d90 according to Figures 1 and 2.

It can be verified that the samples presented a coefficient of variation within the specification according to the USP pharmacopoeia (d10 ≤ 15.0%, d50 ≤ 10.0% e d90 ≤ 15.0%) [21].

The particle size distribution was not responsible for the difference between the two sorbitol raw material samples analyzed.

Figure 1. Particle size distribution of first sample of sorbitol raw material.

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Article

Preformulation Comparative Study between Two Samples of Sorbitol used as Excipient in the Direct Compression Process

Figure 2. Particle size distribution of second sample of sorbitol raw material.

The technique generally used for raw material identification in the pharmaceutical industry is Fourier transform infrared spectroscopy (FTIR) with attenuated total reflectance (ATR) crystals, which is a simple method of API characterization and identification of solid state properties such as polymorphism [22].

It was possible to observe through the technique of vibrational spectroscopy that the first sample of the sorbitol raw material showed a similarity of 88.03% with the standard while the second sample showed a similarity of 65.79% with the standard (Figures 3 and 4). This difference between the spectra obtained from the two sorbitol raw material samples suggests the existence of a polymorphic transition.

Figure 3. Infrared spectrum of first sample of sorbitol raw material.

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Figure 4. Infrared spectrum of second sample of sorbitol raw material.

When evaluating the diffractograms of the two samples of sorbitol raw material it was found that they showed differences, and that the ďŹ rst sample of sorbitol raw material presented the stable gamma polymorphic form, while the second sample presented a mixture of the gamma form and the metastable epsilon form (Figures 5 and 6). The crystal structures of the pure gamma form pattern and the pure epsilon form pattern were obtained from crystallography open database elucidated by references 10 and 11 using the mercury 3.9 software.

Figure 5. XRD spectrum of ďŹ rst sample of sorbitol raw material.

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Preformulation Comparative Study between Two Samples of Sorbitol used as Excipient in the Direct Compression Process

Figure 6. XRD spectrum of second sample of sorbitol raw material.

By analyzing the sorbitol DSC curves (Figures 7 and 8) it was found that the first sample had a welldefined melting point of 99.78 °C because it presented as the stable gamma form, while the second sample had two well-defined melting points at 84.53 ºC and 94.47 ºC, indicating the presence of two polymorphic forms: the stable gamma form and the metastable epsilon form.

Figure 7. DSC curve of first sample of sorbitol raw material.

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Figure 8. DSC curve of second sample of sorbitol raw material.

The fact that sorbitol presents polymorphism makes this compound susceptible to polymorphic transformations when submitted to mechanical shocks, compression forces and micronization. The glass transition is the transition from the amorphous or semi-crystalline state to the rubber state by increasing temperature and always takes place at a lower temperature than the melting point [23]. Thus a metastable polymorphic form having a lower melting point than a stable polymorphic form will also have a lower glass transition temperature than that same more stable polymorphic form [24-28].

Direct compression is a process causing an increase in temperature due to friction, so if the sorbitol raw material with the metastable polymorphic form (lower glass transition temperature) is used, there will be more adhesion in the punch of the compression machine than when a sorbitol raw material with a stable polymorphic form is used [24-28].

CONCLUSIONS There have been few studies about transformations induced by mechanical stresses of pharmaceutical excipients.

Solid-phase changes may impact the physical and chemical stability, dissolution characteristics, in vivo performance (bioavailability, efďŹ cacy, and safety), which is why controlling solid forms during processing is necessary.

Manufacturing processes in the pharmaceutical industry can induce phase transformations and may be responsible for many observed drug product performance problems.

Experiments performed using PSD, FTIR, XRD and DSC techniques have been helpful in the preformulation studies of two sorbitol raw material samples from different manufacturers.

ACKNOWLEDGEMENTS The authors thank EMS Pharmaceutical Industry for the availability of the instruments used in this study.

Manuscript received Jan. 26, 2017; revised manuscript received Apr. 25, 2017; accepted Apr. 27, 2017.

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REFERENCES 1. Kulkarni, S.; Sharma, S.B.; Agrawal, A. Int. J. Pharm. Chem. Biol. Sci., 2015, 5 (2), pp 403-406.

2. Desu, P.K.; Vaishnavi, G.; Divya, K.; Lakshmi, U. Indo Am. J. Pharm. Sci., 2015, 2 (10), pp 1399-1407.

3. Sahitya, G.; Krishnamoorthy, B.; Muthukumaran, M. Int. J. Pharm. Technol., 2013, 4 (4), pp 2311-2331.

4.

Verma, G.; Mishra, M.K. Int. J. Pharma Res. Rev., 2016, 5 (10), pp 12-20.

5. Gore, S.S.; Jagdale, S.C.; Kuchekar, B.S. Int. J. Pharma Sci., 2014, 4 (5), pp 707-712.

6. Tilak, A.; Sharma, R.; Gangwar, S.S.; Verma, M.; Gupta, A.K. J. Biomed. Pharm. Res., 2015, 4 (6), pp 35-45.

7. Vilegave, K.; Vidyasagar, G.; Chandankar, P. Am. J. Pharm. Health Res., 2013, 1 (3), pp 1-20.

8. Patil, J.S.; Marapur, S.C.; Kamalapur, M.V.; Shiralshetti, S.S. Res. J. Pharm. Biol. Chem. Sci., 2010, 1 (3), pp 782-789.

9. Gupta, K.R.; Askarkar, S.S.; Joshi, R.R.; Padole, Y.F. Pharm. Sin., 2015, 6 (4), pp 45-64.

10. Schouten, A.; Kanters, J.A.; Kroon, J.; Comini, S.; Looten, P.; Mathlouthi, M. Carbohydr. Res., 1998, 312, pp 131-137.

11. Rukiah, M.; Lefebvre, J.; Hernandez, O.; Beek, W.V.; Serpelloni, M. J. Appl. Crystallogr., 2004, 37, pp 766-772.

12. Jonas, R.; Silveira, M.M. Appl. Biochem. Biotechnol., 2004, 118, pp 321-336.

13. Willart, J.F.; Lefebvre, J.; Danède, F.; Comini, S.; Looten, P.; Descamps, M. Solid State Commun., 2005, 135, pp 519-524.

14. Garbuio, A.Q.P.; Hanashiro, T.; Markman, B.E.O.; Fonseca, F.L.A.; Perazzo, F.F.; Rosa, P.C.P. J. Appl. Pharm. Sci., 2014, 4 (11), pp 1-7.

15. DiFeo, T.J. Drug Dev. Ind. Pharm., 2003, 29 (9), pp 939-958.

16. Wasylaschuk, W.R.; Harmon, P.A.; Wagner, G.; Harman, A.B.; Templeton, A.C.; Xu, H.; Reed, R.A. J.Pharm. Sci., 2007, 96 (1), pp 106-116.

17. Bukhari, S.N.A.; Hwei, N.S.; Jantan, I. Open Pharmaceutical Sciences Journal, 2015, 2, pp 13 - 20.

18. Sangshetti, J.N.; Deshpande, M.; Zaheer, Z.; Shinde, D.B.; Arote, R. Arabian J. Chem., 2017,10, pp S3412-S3425.

19. Kubavat, H.A.; Shur, J.; Ruecroft, G.; Hipkiss, D.; Price, R. Pharm. Res., 2012, 29, pp 994 - 1006.

20. Liu, L.X.; Marziano, I.; Bentham, A.C.; Litster, J.D.; White, E.T.; Howes, T. Powder Technol., 2013, 240, pp 66-73.

21. US pharmacopeia national formulary. USP 39, Nf 34, volume 1, general chapters {429} Light diffraction measurement of particle size, pp 324-329.

22. Clark, D.; Pysik, A. Handb. Vib. Spectrosc., 2007, pp 1-26.

23. Debenedetti, P.G.; Stillinger, F.H. Nature, 2001, 410, pp 259-267.

24. Bolhuis, G.K.; Rexwinkel, E.G.; Zuurman, K. Drug Dev. Ind. Pharm., 2009, 35 (6), pp 671-677.

25. Li, J.; Wu, Y. Lubricants, 2014, 2 (1), pp 21-43.

26. Abbas, K.A.; Lasekan, O.; Khalil, S.K. Mod. Appl. Sci., 2010, 4 (5), pp 3-21.

27. Karpinski, P.H. Chem. Eng. Technol., 2006, 29 (2), pp 233-237.

Juban, A.; Briancon, S.; Puel, F. Drug Dev. Ind. Pharm., 2016, 42 (11), pp 1857-1864.

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Article

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Powerful and Fast Structural Identification of Pharmaceutical Impurities using Direct Injection Mass Spectrometry and Differential Scanning Calorimetry Renan Marcel Bonilha Dezena1*, José dos Santos Malta Junior1, Eduardo César Meurer2, 3 Marcos Nogueira Eberlin 1 2 EMS Indústria Farmacêutica, Hortolândia, SP, Brazil. Universidade Federal do Paraná, UFPR, 3 Jandaia do Sul, PR, Brazil. Universidade Estadual de Campinas, Unicamp, Campinas, SP, Brazil.

In this work, direct injection mass spectrometry with electrospray positive ion mode has been tested to confirm the possibility of contamination initially detected in loratadine raw material through visual evaluation and differential scanning calorimetry (DSC). MS and MS/MS experiments were performed using a Waters TQD Acquity instrument with an electrospray ionization source with automatic injector. DSC analysis allowed us to confirm the difference in the thermal profile of loratadine raw material and the material of pink appearance, then to corroborate the visual inspection of the raw materials indicating contamination in the loratadine raw material. Pink raw material was submitted to extraction diluted to 10 μg mL-1 in acetonitrile/ water (50:50) with 0.05% formic acid and directly injected to the mass spectrometer (DI-MS). In the single mass spectrum of the pink compound it was possible to verify the presence of the signal at m/z 383 of + protonated loratadine [M+H] and the impurity signal at m/z 865 which was studied by tandem mass spectrometry to access its structural features. Collision-induced dissociation of the ion of m/z 865 resulted in product ions allowing the proposition of two similar structures: the formation of charge transfer complex between loratadine (m/z 383) and a known impurity of loratadine (m/z 482/483) or an ion/molecule reaction producing a covalently bonded compound.

Keywords: Loratadine, direct injection analysis mass spectrometry, differential scanning calorimetry, DSC, active pharmaceutical ingredients, API, impurity profile.

INTRODUCTION Classification and identification of impurities in raw material is essential to the quality control of chemicals in the pharmaceutical industry. Raw materials of drugs are the most important class of chemicals to be evaluated. On their purity depends the pharmacological effect inherent in pharmaceutical formulations.

Qualification of those impurities as present or not present in a raw material demands examination of chemical aspects that involve instrumental analysis. Impurities can usually be classified as organic, inorganic, or residual solvents [1-2].

Organic impurities (OI) are unwanted substances that are sometimes formed during the manufacturing process and storage. OI identification should be carried out to avoid collateral effects that can put in danger people taking the drugs. OI molecules identified can arise from starting materials, by-products, intermediates, degradation products, reagents, ligands and catalysts [1-2].

Concerns over safety of pharmaceutical products and impurity profiles are of increasing importance in drug development and regulatory assessment. Usually most active pharmaceutical ingredients (API) are manufactured by organic chemical syntheses and the major step where the impurity may be produced or observed is in the organic synthesis of the target molecule. Impurities may arise from the starting reagents or from byproducts or degradation during chemical transformations [3-4].

Several components can be formed during such a process. Those components remaining in the final API raw material are considered as impurities. The sources of and routes to the formation of impurities *renan_marcel@hotmail.com

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involve several aspects that require specific assessments for each drug and finished product, such as heat, light, oxidants, changes in the pH of the formulation, trace metal impurities and interactions with packaging components, excipients and other active pharmaceutical ingredients. The degradation reactions that may occur are hydrolysis, oxidation, and photolytic cleavage [5].

Physical properties have a strong impact on a material's bulk properties, product performance, stability and product appearance. Characteristics of a substance that can be realized with the senses are called organoleptic properties, such as physical state (color, odor, transparency and brightness). Melting point, chemical reactivity, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure and density can all be affected. Understanding the physical and chemical properties of the solid pharmaceutical materials might increase the chances of successful drug product and process development [6-9].

There are several situations in pharmaceutical chemistry investigations that can be solved by understanding physical properties measured in macroscopic ways; however, for further development to obtain molecular information and to solve complex problems, the mass spectrometry technique appears to be a strong tool and performs best when linked to MS and MS/MS equipment. Batch analysis of the pharmaceutical product or raw API for product release may require long analysis times. However, electrospray ionization mass spectrometry (ESI-MS) molecular fingerprinting analysis has been demonstrated to be very effective in the rapid structural elucidation of pharmaceutical impurities [10-16].

In this work, mass spectrometry with electrospray positive ion (ESI+) mode has been tested to confirm the possibility of contamination initially detected in loratadine raw materials through visual evaluation of their appearance and Differential Scanning Calorimetry (DSC). The positive mode was used because loratadine is a drug with basic characteristics due to the presence of the nitrogen atom. Consequently, the best analytical condition for this compound is after protonation with formic acid. This result in a more efficient ionization, with better sensitivity to analysis in the ESI+ mode, allowing a greater intensity to evaluate the structure of the formed impurity that possibly also presents basic characteristics. Since the impurity was successfully characterized in positive ion mode the use of negative ion mode was not chosen.

MATERIALS AND METHODS

Reagents Acetonitrile, formic acid and methylene chloride (analytical grade) were obtained from Merck (Darmstadt, Germany) and 2-(2-ethoxyethoxy)ethanol (Transcutol®) was purchased from Gattefosse SA. (Saint Priest, France). Water was purified using Milli-Q Advantage A10 System.

Instrumentation Differential screening calorimetry (DSC) measurements were performed using a Mettler Toledo instrument (Switzerland). The samples were weighed directly in pierced aluminum pans (2.5 - 5 mg) and -1 -1 scanned between 25 ºC and 350 °C at a heating rate of 10 °C min under a nitrogen flow of 80 mL min .

MS and MS/MS experiments were performed using a Waters TQD Acquity/Micromass UK Limited mass spectrometer with an electrospray source (Manchester, England).

LC System equipped with a binary pump was connected to an autosampler (Milford, USA).

Direct injection mass spectrometric condition The mobile phase consisted of acetonitrile/water (60:40) with 0.05% formic acid while the diluent was acetonitrile/water (50:50) with 0.05% formic acid. The flow rate was 0.1 mL min-1 and the temperature of the autosampler was maintained at 15 °C. The DI-MS and DI-MS/MS parameters are presented in Table I.

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Article Table I. DI-MS and DI-MS/MS parameters.

Acquisition Mode Polarity Capillary (kV) Cone (V) Extractor (V) RF (V) Source Temperature (°C) Desolvation Temperature (°C) -1 Cone Gas Flow (L h ) -1 Desolvation Gas Flow (L h ) -1 Collision Gas Flow (mL min ) LM 1 Resolution HM 1 Resolution Ion Energy 1 LM 2 Resolution HM 2 Resolution Ion Energy 2 MS Mode Entrance MS Mode Collision Energy MS Mode Exit

Full Scan

Daughter Scan

ES+ 3.00 30.00 3.00 0.60 120 500 25 500 0.10 10.00 10.00 0.50 10.00 10.00 0.50 50.00 3.00 50.00

ES+ 3.00 30.00 3.00 0.60 120 500 25 500 0.10 15.00 15.00 0.50 15.00 15.00 0.50 1.00 10.00 0.50

RESULTS AND DISCUSSION Loratadine {Ethyl-4-[8-chloro-5,6-dihydro-11H-benzo(5,6)cyclohepta(1,2-b)pyridine]-1-piperidine carboxylate} is a second-generation, non-sedating, long-acting antihistamine which is employed in the symptomatic relief of allergies such as hay fever, urticaria and seasonal allergic rhinitis and it elicits this effect by selective and peripheral antagonistic action on histamine-1 receptors [17-18].

The regular appearance of loratadine raw material is white, but, when visually analyzing a sample of loratadine raw material from a different provider, it was found to be a pink color (Figure 1) not in accordance with the expected appearance, leading to further investigation.

Figure 1. Photo of a loratadine sample showing pink color (left) and another sample of loratadine with white color (normal appearance) (right).

First investigation started with a solubility test in 2-(2-ethoxyethoxy)ethanol (Transcutol®) of a regular loratadine sample and the pink sample, since regular loratadine is not water-soluble. In solution the pink color was better observed while the regular loratadine with white appearance resulted in a clear transparent solution (Figure 2).

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Figure 2. Photo of loratadine raw material presenting pink color (left) and white color solubilized in Transcutol® (2-(2-ethoxyethoxy)ethanol) (right).

Differential Scanning Calorimetry (DSC) was used to compare the difference in the thermal profile of the raw material of loratadine with normal appearance and the sample of loratadine with pink appearance.

Figure 3 shows contamination in the investigated raw material of loratadine (pink).

Figure 3. DSC of loratadine with (A) white appearance and (B) pink appearance.

DSC analysis gave results that confirmed the visual observation of an impurity in the pink material, but the identification was not achieved. To do that it was necessary to extract the pink impurity to perform better identification. First the acid-base properties of loratadine were studied, and using the Henderson-Hasselbach equation [Ionization (%) (α) = 100 − 100 / 1 + antilog (pKa – pH)], with pKa = 5.0 at pH 1.2, giving ionization of 99.9%, led to the conclusion that almost 100% is ionized at pH 1.2 in aqueous media [19].

Figure 4. Extraction of loratadine sample with pink appearance.

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Dezena, R.M.B.; Malta Junior, J.S.; Meurer, E.C.; Eberlin, M.N.

Article After the extraction process the organic phase was evaporated and the DSC analysis of the resulting powder was performed. Overlaying DSC results of purified pink compound with DSC results of pink loratadine sample it was possible to confirm the characteristics of the contaminant in the raw material. The active pharmaceutical ingredient loratadine has a melting point of approximately 140 ºC whereas the pink compound had a melting point of approximately 125 ºC (Figure 5). A plausible explanation would be that although the impurity has a higher molecular mass, it would be less closely packed in its crystalline structure; that is, it has a lower intermolecular interaction and consequently a lower melting point than the loratadine molecule.

Figure 5. DSC of (A) loratadine sample with pink appearance and (B) its isolated impurity.

The final part of the impurity evaluation was the molecular analysis using direct injection mass spectrometry. Solutions of 10 μg mL-1 in acetonitrile/water (50:50) with 0.05% formic acid of the pink isolated impurity and the regular white loratadine raw material were injected in positive ion electrospray ionization (ESI+) mode. Figures 6 and 7 show the results of the injections for the pink isolated impurity and the regular white loratadine raw material.

Figure 6. Mass Spectrum scanning of loratadine raw material with white appearance.

Figure 7. Mass Spectrum scanning of isolated pink compound.

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We might notice in MS spectrum (Figure 6) the predominant signal of the ion of m/z 383 from protonated loratadine ([M+H]+) and (Figure 7) signals at m/z 383 from protonated loratadine and of m/z 865 from the pink impurity which might to be the contaminant present in the pink loratadine raw material. The origin of the ion of m/z 383 in the isolated pink compound MS is from trace amounts of loratadine solution because the extraction process was not fully efficient.

A literature survey reveals that drug substances and drug products are routinely analyzed for impurities and related substances and for assay of active pharmaceutical ingredient (API) content to ensure efficacy and safety of the pharmaceutical product. One of the simplest methods of drug analysis is the formation of charge transfer complexes between the drug acting as electron donor and various electron-deficient reagents acting as electron acceptors. Molecular interactions between electron donors and acceptors are generally associated with the formation of intensely colored charge-transfer complexes [20-22].

In this study it was possible to identify that the color change of loratadine raw material is the formation of a charge-transfer complex. Tandem mass spectrometry experiments were carried out to access information about the structure of the impurity candidate of m/z 865.

Figure 8 shows results of a collision-induced dissociation experiment selecting in the first quadruple the ion of m/z 865 and colliding with argon at 15 eV in the collision cell, and scanning the last quadrupole mass analyzer from m/z 50 to m/z 900 mass range.

Figure 8. Mass Spectrum fragmentation of m/z 865 ion.

Fragments of m/z 483 and m/z 383 suggest a precursor ion formed by a proton dimer of loratadine and the impurity, and we suggest the ion of m/z 482 is the molecular ion of the impurity resulting from an electron transfer from the zwitterionic impurity part to the protonated loratadine, as shown in Scheme 1.

Scheme 1 32

Dezena, R.M.B.; Malta Junior, J.S.; Meurer, E.C.; Eberlin, M.N.

Article The charge transfer complex (of m/z 865) dissociates to generate a distonic ion of m/z 482 (open shell species), which is a perfectly plausible phenomenon to occur in gas phase ionization [23]. Figure 9 shows the suggested structure for the impurity as a charge transfer complex that seems to be corroborated by the tandem mass experiment.

Figure 9. Suggested structure of charge-transfer complex.

Another possible structure for the formation of pink impurity with m/z 865 in the sample of loratadine raw material would be a covalent bond between the negative oxygen of the known impurity and the electrophilic carbon connected to the nitrogen of the loratadine molecule, formed by an ion/molecule reaction between the impurity and loratadine (Figure 10).

Figure 10. Suggested structure of covalent bond between the negative oxygen of the known impurity and the electrophilic carbon connected to the nitrogen of the loratadine molecule.

We might observe that either proposed impurity ion would give us the same experimental results, but the charge-transfer ion is often proposed for colored species in pharmaceutical analysis [24].

CONCLUSIONS The results obtained demonstrated that by associating different analytical techniques was possible to control the quality of loratadine raw material, and mass spectrometry using ESI positive mode has become an important analytical methodology in the quality control laboratory for structural identiďŹ cation of pharmaceutical samples.

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Article

ACKNOWLEDGEMENTS The authors thank EMS Pharmaceutical Industry for the availability of the instruments used in this study. th

nd

Manuscript received Dec. 1, 2016; 1 round revised received Apr. 12, 2017; 2 round revised received May 13, 2017; accepted May 18, 2017.

Article

REFERENCES 1. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Tripartite Guideline). Impurities in new drug substances Q3A(R2). 25 October 2006.

2. Resolução RDC nº 53, de 04 de dezembro de 2015. Agência nacional de vigilância sanitária. Ministério da saúde, Brasil. Estabelece parâmetros para a notificação, identificação e qualificação de produtos de degradação em medicamentos com substâncias ativas sintéticas e semissintéticas, classificados como novos, genéricos e similares, e dá outras providências. Diário oficial da união. Brasília, 08 Dec. 2015.

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3. Pires, S.A.; Mota, L.M.; Garcia, J.S.; Amaral, P.H.; Meurer, E.C.; Eberlin, M.N.; Trevisan, M.G. Braz. J. Pharm. Sci., 2015, 51 (4) pp 840-845.

4. Gonçalves, A.R.; Nascimento, H.L.D.; Duarte, G.H.B.; Simas, R.C.; Soares, A.D.J.; Eberlin, M.N.; Marques, L.A. Chromatographia, 2016, 79 (13), pp 841-849.

5. Prabu, S.L; Suriyaprakash, T.N.K. Int. J. Pharm. Sci. Rev. Res., 2010, 3 (2), pp 66-71.

6. Gore, S.S.; Jagdale, S.C.; Kuchekar, B. S. Int. J. Pharma. Sci., 2014, 4 (5), pp 707-712.

7. Kulkarni, S.; Sharma, S. B.; Agrawal, A. Int. J. Pharm., Chem. Biol. Sci., 2015, 5 (2), pp 403-406.

8. Sahitya, G.; Krishnamoorthy, B.; Muthukumaran, M. Int. J. Pharm. Technol., 2013, 4 (4), pp 2311-2331.

9. Desu, P.K.; Vaishnavi, G.; Divya, K.; Lakshmi, U. Indo Am. J. Pharm. Sci., 2015, 2 (10), pp 1399-1407.

10. Li, M.; Wang, X.; Chen, B.; Lin, M.; Buevich, A.V.; Chan, T.M.; Rustum, A.M. Rapid Commun. Mass Spectrom., 2009, 23, pp 3533–3542.

11. Souza, P.P.D.; Siebald, H.G.L.; Augusti, D.V.; Neto, W.B.; Amorim, V.M.; Catharino, R.R.; Eberlin, M.N.; Augusti, R. J. Agric. Food Chem., 2007, 55, pp 2094-2102.

12. Schiozer, A.L.; Cabral, E.C.; Godoy, L.A.F.D.; Chaves, F.C.M.; Poppi, R.J.; Riveros, J.M.; Eberlin, M.N.; Barata, L.E.S. J. Braz. Chem. Soc., 2012, 23 (3), pp 409-414.

13. Araújo, A.S.; Rocha, L.L.D.; Tomazela, D.M.; Sawaya, A.C.H.F.; Almeida, R.R.; Catharino, R.R.; Eberlin, M.N. Analyst, 2005, 130, pp 884–889.

14. Plumb, R.S.; Jones, M.D.; Rainville, P.D.; Nicholson, J.K. J. Chromatogr. Sci., 2008, 46, pp 193-198.

15. Li, M.; Lin, M.; Rustum, A. J. Pharm. Biomed. Anal., 2008, 48, pp 1451-1456.

16. Bu, X.; Yang, J.; Gong, X.; Welch, C.J. J. Pharm. Biomed. Anal., 2014, 94, pp 139-144.

17. Roman, I.J.; Danzig, M.R. Clin. Rev. Allergy, 1993, 11 (1), pp 89-110.

18. Picard, N.; Dridi, D.; Sauvage, F.L.; Boughattas, N.A.; Marquet, P. J. Sep. Sci., 2009, 32, pp 22092217.

19. Hancu, G.; Campian, C.; Rusu, A.; Mircia, E.; Kelemen, H. Adv. Pharm. Bull. 2014, 4 (2) pp 161-165.

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Technical Note

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On the Feasibility of Spectroscopy and Curve Resolution to Detection of Ethinylestradiol in Sewage – Preliminary studies Suzana Moreira Muniz Curti, Cíntia Maria Ritter, Letícia Braga da Silva, Leonardo Valderrama, Marcilene Ferrari Barriquello Consolin, Nelson Consolin Filho, Flávia Vieira da Silva Medeiros, Paulo Henrique Março and Patrícia Valderrama* Universidade Tecnológica Federal do Paraná (UTFPR), C.P. 271, CEP 87301-899, Campo Mourão, PR, Brazil The synthetic estrogen ethinylestradiol (EE) is an active component present in oral contraceptives, being considered as an endocrine disrupting compound and an emerging pollutant. It is excreted from humans and released via sewage treatment effluents into aquatic environments. In order to detect EE in sewage, sample were collected in different sewage treatment (ST) locations to be measured trough ultraviolet-visible spectroscopy (200-900 nm) coupled with Multivariate Curve Resolution Alternating Least Squares (MCR-ALS), by using the strategy of column augmentation. Independent Component Analysis (ICA) was used to provide initial estimative to MCR-ALS. The study was carried out during three months (March, April and May, 2012) in three different collecting places. Pure spectra and kinetic of the EE present at ST were recovered by MCR-ALS, being the one attributed to the EE identical to the reported in the literature. Other substances named as interferents were also detected but not identified and the spectra and kinetics were recovered.

Keywords: Ethinylestradiol, Molecular spectroscopy, Curve resolution, Sewage INTRODUCTION Emerging pollutants have gained importance based on their persistence and potential risk once they enter the environment [1]. A significant number of emerging pollutants resulting from point and diffuse pollution is present in the aquatic environment. These are chemicals that are not commonly monitored but have the potential to enter the environment and cause adverse ecological and human health effects [2].

This emerging pollutants class can include hormones, mainly used as contraceptives, like ethinylestradiol.

Ethinylestradiol (19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol, EE) is an active component present in oral contraceptives, being considered as an endocrine disrupting compound. It is excreted from humans and released via sewage treatment (ST) effluents into aquatic environments [3].

EE apparently affects the phosphate cycle indicated by the increasing phosphate concentrations in water [4]. Any chemical environmental pollutant incorporated into an organism has potential to affect the hormonal balance of a species including humans. Then, the detection of EE in the environment is gaining significant importance when evaluating water quality [3]. In a try to detect this substance in aqueous matrices, previous studies have shown the application of some methodologies as Enzyme-Linked Immunosorbent Assays (ELISA) [5], immunoassays [6], electrochemical [3], adsorption mechanisms [7,8], solid-phase microextraction and gas chromatography–mass spectrometry [9]. However, these methods demands considerable amount of reagents and solvents, besides sample preparation and in many cases instruments and or systems which are expensive and require a lot of practice to be correctly operated.

Considering these issues, the aim of this paper is propose an alternative methodology to detect EE in ST based on ultraviolet-visible (UV-Vis) spectroscopy and chemometric methods of curve resolution.

In order to apply the Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS) the matrices can be concatenated one on top of the other in the new augmented matrix Daugment. This method of matrix augmentation allows the analysis of the variability among samples in Daugment and summarises the information in the data with respect of their spectra variation [10]. *patriciav@utfpr.edu.br / pativalderrama@gmail.com

35

On the Feasibility of Spectroscopy and Curve Resolution to Detection of Ethinylestradiol in Sewage – Preliminary studies

Technical Note

According to the bilinear model, the augmented data matrix Daugment is decomposed in the product of two matrices, one augmented matrix describing respectively the different row spaces Caugment of the original individual data matrices, and one matrix describing the common column spectra space ST of them, as shown the following equation [10]: T

Daugment = CaugmentS + Eaugment(1) were Eaugment gives the spectral variation not explained by the bilinear model MCR-ALS is a bilinear model which assumes that the observed spectra are a linear combination of the spectra from pure components in the system [11]. The algorithm steps include determining the number of components in Daugment by rank analysis methods such as Principal Component Analysis by observing the percentage of explained variance [10] or by regarding its Loadings [12]. Then, an initial estimative of concentrations (Caugment) or spectra matrix (ST) containing as many profiles as the number of components estimated for Daugment is constructed to start the iterative resolution process. Here, the initial estimative to ST was determined through ICA scores, performed by JADE algorithm [13,14]. Those initial estimates of T the concentration profiles Caugment and pure species spectra S are optimized by solving Equation (1) iteratively by alternating least squares (ALS) optimization.

The drawback intrinsic in all of the resolution methods are related to the rotational ambiguity. So, in order to reach the best results, constraints may be applied during optimization steps to provide meaningful T shapes for the Caugment and S profiles. These constraints may result in answers which are closer to the real ones depending on previous knowledge about chemical or mathematical properties that Caugment and/or ST profiles must fulfill, and so calculated profiles are modified so that they obey the constraint condition(s) [15]. In MCR-ALS, any type of constraint, such as non-negativity, unimodality, closure, selective concentration can be easily applied to the solutions sought [16].

MATERIALS AND METHODS Sample from three different locations of the treatment were collected in two different ST. The study was carried out during three months (March, April and May, 2012), being collected two samples/month at three different collecting points each day.

Sampling was done each week, being handled by technical support from Paraná State Sanitation Company (SANEPAR). The first sampling point was located at the entrance of the raw sewage, while second sampling point was just after a pre-treatment step, precisely by the side of an anaerobic fluidic sludge reactor, and third and last located after treatment, where effluent is ready to be released into the water bulk.

For analysis, 25 mg of the filtrate obtained from effluent originated from the ST was dissolved in absolute ethanol (Vetec), according to the methodology described in the Brazilian Pharmacopeia for dosing the EE [17].

The spectra of these prepared samples were acquired at a PG Instrument Ltd spectrometer, model T80+, in the range from 200 to 900 nm (steps of 1 nm) in a 10 mm quartz cuvette.

-1 A standard solution of EE (Sigma) was obtained in absolute ethanol (Vetec) (26 g mL ). The absolute ethanol was employed to obtain the standard solution of EE because this solvent was also employed for the sewage sample preparation, and it is the solvent suggested by the Brazilian Pharmacopeia [17]. A spectrum of this solution was acquired on the same spectral conditions.

Data were analyzed using MATLAB version R2007b (The Mathworks Inc., MA, USA) where chemometric curve resolution was performed by Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS).

The MCR-ALS algorithm code and graphical user interface for MATLAB [18] are freely available from the home page of MCR at http://www.mcrals.info/. Independent Component Analysis (ICA) with Joint Approximate Diagonalization of Eigenmatrices (JADE) algorithm [13] was used as initial estimative to start MCR-ALS resolution [14].

36

Curti, S.M.M.; Ritter, C.M.; Silva, L.B. da; Valderrama, L.; Consolin, M.F.B.; Consolin Filho, N.; Medeiros, F.V.S.; Março, P.H.; Valderrama, P.

Technical Note

In this work, the individual k data matrices of dimensions Dk(I, J), where (I = 3 spectra and J = 701 wavelengths), obtained at March 27 and 29, April 24 and 26, May 17 and 24, 2012, were concatenated one on top of the other in the new augmented matrix Daugment, generating a new matrix with dimensions of (18 x 701). The constraint used in this study was only non-negativity for the concentration and spectra.

RESULTS AND DISCUSSION In order to have an initial estimation of the number of species, the chemical or pseudorank (mathematical rank in absence of experimental noise) of the data matrix Daugment was estimated using PCA [10]. The first four Principal Components (PC's) represented 99.90% of the explained variance (98.27% in PC1, 1.13% in PC2, 0.39% in PC3 and 0.11% in PC4). Therefore, the chemical or pseudorank utilized to MCR-ALS was four.

The next step was to make an initial estimative for C containing as many profiles as the number of components estimated by PCA. Here, the initial C was determined using ICA that promotes the minimization of the statistical dependence of the signals. So, by using ICA no problems of drawback (necessity of the presence of “pure” variables) presented by the most commonly used algorithm [19], as well, no problem of local minimum instead of global minimum by MCR-ALS occurs. Once the initial estimative was generated, the iterative optimization step was started, under constraints of non negativity for C and ST, performed by alternating least squares.

The schematic results obtained by applying curve resolution at UV-Vis spectroscopy data from sewage is presented in Figure 1. The UV-Vis spectra of all prepared samples collected from last point of the sewage treatment is shown in Figure 1(A). The pure spectra and concentration profiles (relative concentration) of the four different components present in the UV-Vis spectra are given in detail at Figure 1(B) and (C), respectively. Figure 1(D) present the molecular structure of ethinylesradiol, while Figure 1 (E) shows the UV-Vis spectra of standard EE. From this plot, it was possible to detect the ethinylestradiol and other chemical components spectra [Figure 1(B)], and its relative concentration related to each collecting day [Figure 1(C)]. However, as EE is the mainly analyte objective of this article, the others spectral and relative concentration profiles are shown, but not discussed here. th

By looking at Figure 1(C), it shows that at April 26 there is a total disappearing of the pollutants. This can be explained by a huge rain that took place over Campo Mourão, what can be checked through INMET webpage (National Institute of Meteorology) [20], showing an amount of 263.0 mm of water, which is twofold above the average. The consequence was a significant dilution in sample solutions, turning its constituent's concentrations below the detection limit of the instrument, even though those substances may be present at that day.

Figure 1. (A) UV-Vis spectra of all samples collected from sewage treatment. (B) Pure spectra and (C) Relative concentration recovered by MCR-ALS using ICA as initial estimative. (—) ethinylestradiol; (---) interferent 1; ( ) interferent 2; (---) interferent 3. (D) Molecular structure of ethinylestradiol. (E) UV-Vis spectra from standard ethinylestradiol in absolute ethanol (26 g mL-1).

37

On the Feasibility of Spectroscopy and Curve Resolution to Detection of Ethinylestradiol in Sewage – Preliminary studies

Technical Note

The spectra recovered by MCR-ALS in the Figure 1(B) suggest that one component can be the ethinylestradiol. The recovered spectra was in accordance with previous spectra presented in the literature [21], being also in agreement to the Brazilian Pharmacopeia [17]. The other chemical constituents were named as interferents 1, 2 and 3, respectively. According to He et al. [22], the interferent 1 may be characterized as being organic matter. However, the UV-Vis spectroscopy present a lack of selectivity and certainly, other species can be absorbed in the same region of this interferent. The interferents 2 and 3 were not identified. Nevertheless, notably, another important aspect of curves resolution applied to spectroscopic data is the ability to assess a particular species in the presence of any interferents. These results suggest that UV-Vis spectroscopy coupled with resolution methods can be able to identify pollutants in sewage.

CONCLUSIONS Identification of pollutants in sewage was accessed through UV-Vis spectroscopy and chemometric methods of curve resolution. The results show that UV-Vis spectroscopy data set evaluated trough ICA as initial estimative to MCR-ALS analysis were able to light up about those residues quantities by the observation of the relative concentration. Even being a preliminary study, the results show the potentiality of spectroscopy coupled with curve resolution to monitor pollutants in sewage. Certainly, a validation using a chromatographic method could leave the study more conclusive and is a future prospect. However, the spectroscopy has advantages as the quickness, does not require sample preparation, and does not produces toxic residues (which is in accordance with the green chemistry requirements), besides being relatively low cost.

REFERENCES 1. Barrios, J.A.; Becerril, E.; De Léon, C.; Barrera-Díaz, C.; Jiménez, B. Fuel, 2015, 149, pp 26-33.

2. Geissen, V.; Mol, H.; Klumpp, E.; Umlauf, G.; Nadal, M.; van der Ploeg, M.; van de Zee, S.E.A.T.M.; Ritsema, C.J. Int. Soil Water Cons. Res., 2015, 3, pp 57-65.

3. Martínez, N.A.; Pereira, S.V.; Bertolino, F.A.; Schneider, R.J.; Messina, G.A.; Raba, J. Anal. Chim.

Acta, 2012, 723, pp 27-32.

4. Schramm, K.W.; Jaser, W.; Welzl, G.; Pfister, G.; Wöhler-Moorhoff, G.F.; Hense, B.A. Ecotoxicol.

Environ. Saf., 2008, 69, pp 437-452.

5. Silva, C.P.; Lima, D.L.D.; Schneider, R.J.; Otero, M.; Esteves, V.I. J. Environ. Manage., 2013, 124, pp 121-127.

6. Hintemann, T.; Schneider, C.; Schöler, H.F.; Schneider, R.J. Water Res., 2006, 40, pp 2287-2294.

7. Han, J.; Qiu, W.; Meng, S.; Gao, W. Water Res., 2012, 46, pp 5715-5724.

8. Han, J.; Qiu, W.; Cao, Z.; Hu, J.; Gao, W. Water Res., 2013, 47, pp 2273-2284.

9. Braun, P.; Moeder, M.; Schrader, St.; Popp, P.; Kuschk, P.; Engewald, W. J. Chromatogr. B, 2003, 988, pp 41-51.

10. Março, P.H.; Poppi, R.J.; Scarminio, I.S.; Tauler, R. Food Chem., 2011, 125, pp 1020-1027.

11. Piqueras, S.; Duponchel, L.; Tauler, R.; de Juan, A. Anal. Chim. Acta, 2011, 705, pp 182-192.

12. Valderrama, P.; Março, P.H.; Locquet, N.; Ammari, F.; Rutledge, D.N. Chemom. Intell. Lab. Syst., 2011, 106, pp 166-172.

13. Cardoso, J.F.; Soulomiac, A. IEE Procedings-F, 1993, 140, pp. 362-370. Available from: http://people.ee.duke.edu/~lcarin/Cardoso_IEE.pdf [Acessed 12 March 2017].

38

On the Feasibility of Spectroscopy and Curve Resolution to Detection of Ethinylestradiol in Sewage – Preliminary studies

Curti, S.M.M.; Ritter, C.M.; Silva, L.B. da; Valderrama, L.; Consolin, M.F.B.; Consolin Filho, N.; Medeiros, F.V.S.; Março, P.H.; Valderrama, P.

1. Valderrama, L.; Gonçalves, R.P.; Março, P.H.; Rutledge, D.N.; Valderrama, P. J. Adv. Res., 14.

2016, 7, pp 795-802.

15.

2. Jayaramana, A.; Mas, S.; Tauler, R.; de Juan, A. J. Chromatogr. B, 2012, 910, pp 138-148.

3. Março, P.H.; Valderrama, P.; Alexandrino, G.L.; Poppi, R.J.; Tauler, R. Quim. Nova, 2014, 37, pp 16.

1525-1532.

4. http://www.anvisa.gov.br/hotsite/cd_farmacopeia/pdf/volume2.pdf [acessed 12 March 2017].

17.

5. Jaumot, J.; de Juan, A.; Tauler, R. Chemom. Intell. Lab. Syst., 2015, 140, pp 1-12.

18.

19.

6. Manakhova, Y.B.; Astakhov, A.A.; Mushtakova, S.P.; Gribov. L.A.; J. Anal. Chem., 2011, 66, pp 351-362.

20. http://www.inmet.gov.br/portal/arq/upload/BOLETIM-AGRO_MENSAL_201204.pdf [Acessed 12 7.

March 2017].

21. Nevado, J.J.B.; Flores, J.R.; Peñalvo, G.C. Anal. Chim. Acta, 1997, 340, pp 257-265.

8.

9.

22. He, X.S.; Xi, B.D.; Wei, Z.M.; Jiang, Y.H.; Geng, C.M.; Yang, Y.; Yuan, Y.; Liu, H. L. Bioresour.

Technol., 2011, 102, pp 2322-2327.

39

Br. J. Anal. Chem., 2017, 4 (15), pp 40-44

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Combustion Ion Chromatography - Enhancing Halogen Detection Using Preconcentration Methods 1

1

2

Adelon Agustin , Mark Manahan , Bernard G. Sheldon 1

Cosa Xentaur, Yaphank, NY, USA; 2Thermo Fisher Scientific, Sunnyvale, CA, USA

The purpose of this study is to demonstrate the method sensitivity of adding sample preconcentration to Combustion Ion Chromatography. Samples were combusted in a Mitsubishi AQF2100H furnace equipped with a GA210 sparging unit. One mL samples were transferred to an anion ™ ™ concentrator column mounted on the injection valve of a Thermo Scientific Dionex ICS-Integrion ™ ™ Integrated Reagent-Free Ion Chromatography (RFIC ) system. The anion analysis was performed ™ ™ ™ using a Thermo Scientific Dionex IonPac AS15 column. Limit of detection for the anions determined by combustion ion chromatography (IC) was shown to be as low as approximately 10 ppb, with limits of quantitation being approximately 25 ppb. Outstanding retention time stability (0.08% RSD for chloride) was also demonstrated.

Keywords: Combustion Ion Chromatography, sample preconcentration, halogens and sulfate analysis.

INTRODUCTION Combustion can be used to oxidize a sample so that the combustion products can be analyzed and the sample composition determined. Combustion of organic samples for CHN analysis is a technique with a long and rich history [1,2]. Combustion may also be used to prepare samples for halogen and sulfur content analysis. Under high temperature oxidizing conditions, the halogens are converted to volatile HX and X2 and the sulfur to SOx. These volatile products are trapped in an aqueous solution which can subsequently be analyzed by ion chromatography to give the concentrations of the individual halides. The sulfur species are further oxidized in solution and sulfate is determined by IC. Combustion of samples for halogen and sulfur content has been practiced for years, using techniques such as oxygen bombs (Parr, etc.), Schöniger flasks and the Wickbold apparatus. In some cases such as oxygen bombs the heat is derived internally, via chemical reaction. In open tube methods such as the Wickbold apparatus, heat is applied externally. Recently microwave ovens have been used to heat the sample. All of these methods require the manual transfer of the sample into a reaction vessel and, after combustion, from the vessel to the ion chromatograph. In many cases they require extensive methods development to optimize the combustion conditions. In addition the closed vessel approaches are inherently labor intensive, slow and require skilled operators to perform them.

Automation of the combustion process is now available using apparatus from several manufacturers, including Mitsubishi Analytech, Inc. The AQF-2100 from Mitsubishi is comprised of an autosampler designed to handle the particular physical form of the sample, the combustion furnace and controller, and the absorption unit which includes a sample injection valve. Gases, liquids and solid samples can all be managed with the appropriate autosampler. Solids and semi-solid samples are placed in a quartz sample boat and pushed into the hot quartz tube furnace. Figure 1 shows a schematic of the combustion apparatus.

Combustion ion chromatography is an inherently dilutive technique, with a relatively small amount of sample gases being trapped in a relatively larger volume of water, resulting in low analyte concentrations in the injection sample. In addition, sulfate analysis requires the addition of hydrogen peroxide to the sparger water, to oxidize to sulfate the various sulfur species produced. The peroxide will sometimes 40

Combustion Ion Chromatography - Enhancing Halogen Detection Using Preconcentration Methods

Sponsor Report

interfere with the fluoride peak in the ion chromatograms.

There are several potential solutions to these problems. Initial sample size can be increased but is limited by the combustion capability of the system to about 100 mg; sometimes as much as 500 mg can be used. Volumes injected into the IC can be increased, but these too have practical limits and applications limitations. For instance unusually large sample volumes can cause problems for fluoride quantitation due to the increased size of the adjacent water dip. The solution studied in this work is to adapt sample preconcentration methodology for ion chromatography to this application.

Figure 1. Diagram of a combustion ion chromatography system.

MATERIALS AND METHODS Equipment Combustion apparatus: Mitsubishi Chemical Analytech AQF-2100H including ASC-250L liquid sample changer, ABC-210 automatic boat controller, HF-210 horizontal furnace and GA-210 sample absorption unit with 1 mL sample loop.

Combustion samples: 90 µL xylene solutions.

Ion Chromatograph: Dionex ICS-Integrion system Column: Dionex IonPac AG15 and AS15 column set, 4 x 250 mm; Column Temperature: 30 °C Eluent: 33.5 mM KOH, from Thermo Scientific Dionex EGC-KOH Eluent Generator Cartridge -1 Flow Rate: 1.2 mL min Concentrator Column: UTAC-XLP1 Sample transfer: Thermo Scientific Dionex AXP Auxiliary Pump with a Dionex ATC-HCAnion Trap -1 Column, 1 mL min Detection: Suppressed conductivity, Thermo Scientific™ Dionex™ ASRS™ 300 Anion Self-Regenerating Suppressor, 4 mm, 100 mA current, recycle mode, detector temperature 35 °C

Figure 2. Combustion ion chromatograph.

41

Agustin, A.; Manahan, M.; Sheldon, B.G.

Sponsor Report Samples were combusted using standard methods and the resulting volatile components absorbed into 3 mL of deionized (DI) water with hydrogen peroxide. The sparger fluid was loaded into a 1 mL sample loop on the GA-210 valve using the fluidics on board the GA-210. Loop contents were transferred to the concentrator column using an AXP pump. See Figure 3 for a plumbing schematic.

Figure 3. Schematic, principal fluidics pathways.

RESULTS Blank runs of sample solvent were compared to those obtained by running the sample combustion with an empty sample boat. Low background levels of fluoride, chloride and sulfate were detected, with no appreciable difference between the empty boat and solvent. This demonstrates that the background is potentially due to low level contamination of the sparger water, transfer water or plumbing.

Note the early elution section of the blank chromatograms in Figure 4, in the expanded section above.

The combined performance of the column and chromatograph provide for excellent separation between the fluoride and the water dip, as well as the peak, probably peroxide, which precedes fluoride. In addition, the fluoride is well resolved from the trailing peaks, likely to be acetate and formate which are frequently observed in combustion IC. The result of this high resolution is to afford quantitative results for fluoride which are less than 1% RSD for repeat sample injections. The highly reproducible chromatography along with the high resolution as provides confidence in assigning the identity of fluoride to an individual peak.

Figure 4. Blank injections, solvent blank (blue trace) compared to an empty sample boat.

Standards were prepared in xylene, combusted before absorption and absorbed into aqueous hydrogen peroxide. One mL aliquots were passed through a concentrator column and analyzed on the ion chromatograph. Figure 5 demonstrates the 5-fold improvement in signal size resulting from the sample preconcentration.

42

Combustion Ion Chromatography - Enhancing Halogen Detection Using Preconcentration Methods

Sponsor Report

Figure 5. Overlaid 10 ppb standards: 0.2 mL direct injection vs. 1 mL concentrated.

Figure 6. Overlaid standards: 0, 10, 50, 100 Îźg L-1.

The excellent run to run reproducibility of 0.08% RSD for the method is shown in Figure 7 where consecutive, repeat injections of a low concentration sample (approximately 50 ppb) are compared. Table I shows the improvement in the quantitation for uoride afforded by the increased sample size from sample preconcentration. The table compares the reproducibility of area and height measurements for direct injection and pre-concentrated samples. Since sample volumes have been increased by a factor of ďŹ ve, peak areas and heights are proportionally increased. This provides for improved reliability of peak integration and signal to noise, both of which reduce the variability of the quantitation.

Figure 7. Overlaid repeat injections of the same sample.

43

Agustin, A.; Manahan, M.; Sheldon, B.G.

Sponsor Report Table I. Area and height reproducibility for fluoride; direct injection compared to sample preconcentration.

Direct Injection, 0.2 mL

Preconcentration, 1 mL

Area (μS*min)

Height (μS)

Area (μS*min)

Height (μS)

Run 1

0.01612

0.1366

0.06049

0.5733

Run 2

0.01533

0.1335

0.06034

0.5711

Run 3

0.01666

0.1369

0.06034

0.5720

Standard Deviation

0.00072

0.0000

0.00011

0.0000

4.19%

1.38%

0.15%

0.20%

% Relative Standard Deviation

CONCLUSIONS Combustion ion chromatography automates the analysis of halogens and sulfate in difficult to process samples.

The combination of the high performance Dionex IonPac AS15 column and the Dionex ICS-Integrion system provides superior resolution and reproducibility - as low as 0.08% RSD. Sample preconcentration provides significant improvements in quantitation of low concentration samples.

Future work may evaluate smaller sample trapping volumes, approaches to ultrahigh purity transfer solutions, increased sample concentration volumes and faster ion chromatography methods.

ACKNOWLEDGEMENTS The provision of data and experimental methods by Mark Manahan and Adelon Agustin of COSA+ Xentaur is gratefully acknowledged. Kirk Chassaniol of Thermo Fisher Scientific provided valuable assistance.

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This sponsor report is the responsibility of Thermo Fisher Scientific.

REFERENCES nd

1. Niederl, J.B; Niederl, V. Micromethods of Quantitative Organic Analysis, 2 Edition, John Wiley, 1942.

2. Strouts, C.R.N; Gilfillan, J.H.; Wilson, H.N. Chapter 14. Analytical Chemistry; Vol 1; Oxford University Press, 1955.

44

Br. J. Anal. Chem., 2017, 4 (15), pp 45-48

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Determination of Trace Elements in Naphtha using ICP OES 1

Bruno Menezes Siqueira , Sanja Asendorf 1

2

Nova Analítica Importação e Exportação, São Paulo, SP, BR 2 Thermo Fisher Scientific, Bremen, Germany

A method of elemental determination of Ag, Al, As, B, Ba, Ca, Cd, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Na, Ni, P, Pb, Si, Sn, Ti, V, Zn in naphtha samples was developed using ICP OES (in radial view) with a cooling down spray chamber. With this spray chamber, it is possible to cool the spray down to temperatures as low as -10 °C. This reduces the solvent load on the plasma and allows straight forward analysis of organic solvents with a more stable plasma and reduced background emission. Auxiliary and nebulizer gas was optimized for better conditions for aspirating organic solvent. The limits of detection obtained in ICP OES for of Ag, Al, As, B, Ba, Ca, Cd, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Na, Ni, P, Pb, Si, Sn, Ti, V, and Zn were 3.4, 7.9, 7.4, 13, 0.2, 0.1, 0.6, 1.0, 1.3, 1.9, 2.7, 0.04, 0.3, 2.7, 10, 1.6, 11, 7.6, 8.0, 8.1, 0.4, 1.0, and 0.4 respectively.

Keywords: naphtha, cool down spray chamber, organic solvents, elemental determination, ICP OES INTRODUCTION The analysis of organic solvents by Inductively Coupled Plasma – Optical Emission Spectroscopy (ICP-OES) is often seen as problematic, especially when the solvents are volatile. Typically, a volatile solvent (with respect to ICP-OES) is defined as a solvent which exhibits a vapor pressure of greater than 30 mm Hg. When a volatile solvent such as naphtha is introduced into an ICP, the sample transport efficiency is much greater than that with aqueous samples and this can lead to undesirable effects such as plasma instability. To introduce a solvent, such as naphtha, into the plasma, the volatility must first be reduced. This can be done in two ways; either by dilution with a less volatile solvent such as kerosene, or by cooling the solvent prior to introduction into the plasma which is typically done using a cooled spray chamber. As the first option will degrade the sensitivity of the analysis, the second of these two options is preferable [1,2].

Among the various petroleum derivatives, which are obtained after their fractionation, there is naphtha.

Naphtha is a colorless liquid with a distillation range close to gasoline and which comprises a range of C4 to C15 hydrocarbons. It is used in the production of gasoline and as raw material of the petrochemical industry in the production of ethylene and propylene, in addition to other liquid fractions such as benzene, toluene and xylene [3,4].

The analysis of trace elements in naphtha is important in petrochemical industry, especially in the cracking of hydrocarbons. The presence of trace elements can severely hamper this process as well as poison the catalysts used, which are often expensive. One example is arsenic (in the form of arsine), which can poison catalysts at trace concentrations (as low as 50 μg kg-1). In addition, arsenic can cause problems with high temperature naphtha cracking tubes due to the formation of coke build-up. This build-up can result in the eventual failure of the tubes and subsequently reduce the production capabilities. Arsenic free naphtha is also the preferred feedstock for a number of downstream processes such as catalytic reforming, gasoline blending, and C5 and C6 isomerization. These processes are using platinum and palladium catalysts where the presence of arsenic would cause serious problems, poisoning the catalysts.

*bruno.menezes@novanalitica.com.br 45

Determination of Trace Elements in Naphtha using ICP OES

Sponsor Report MATERIALS AND METHODS Sample Preparation -1

Calibration standards were prepared by diluting oil based standards S21-K 100 mg kg (elements contained within the standard listed in Table III), As 100 mg kg-1 and Hg 100 mg kg-1 (Conostan, from SCP SCIENCE) on weight basis in naphtha (from Fisher Scientific™) to concentrations shown in Table I. A calibration blank was prepared from naphtha and a further blank was spiked (Table I) using the same standards as for the calibration.

Table I. Concentration of calibration solutions and spiked blank

Solution

Concentration (mg kg -1) S-21 + K

As

Hg

Low Standard

0.96

0.95

0.97

High Stardard

4.88

4.90

4.89

Spike

2.34

2.37

2.36

Elemental determination The Thermo Scientific™ iCAP™ 7600 ICP-OES Radial was used for this analysis. The radial system was chosen because the interferences from carbon based emissions can be reduced by optimizing the radial viewing height. The GE IsoMist™ is a Peltier cooled spray chamber which was used in conjunction with a glass concentric nebulizer for this analysis.

The GE IsoMist was set to -10 °C to reduce the volatility of the samples to be within the range of the plasma load that the instrument can handle. Naphtha was then aspirated into the IsoMist and the plasma position in relation to the coil was observed. The auxiliary gas flow was adjusted until the base of the plasma was half way between the top of the auxiliary tube and the base of the load coil. The nebulizer gas flow was adjusted until the green sample channel was just below the top of the torch. The radial viewing height was adjusted to the height that gave the best signal-to-background ratio for all of the elements to be analyzed. Associated plasma gas settings for sample introduction are shown in Table II. Table II. Instrument Parameters

46

Parameter

Setting

Pump Speed

40 rpm

Nebulizer

Glass concentric

Nebulizer Gas Flow

0.45 L min

Auxiliary Gas

1.5 L min

Coolant Gas Flow

12 L min

Center Tube

1.5 mm

RF Power

1150 W

Radial Viewing Height

8 mm

Exposure Time

UV 15 s, Vis 5 s

-1

-1

-1

Siqueira, B.M; Asendorf, S.

Sponsor Report RESULTS AND DISCUSSION The instrument was calibrated and the spiked blank was analyzed and the recovery calculated. A detection limit study was carried out by analyzing the calibration blank with ten replicates and multiplying the standard deviation of this analysis by three. For each element, wavelengths were selected using the intuitive wavelength selection tool of the Thermo Scientific™ Qtegra™ Intelligent Scientific Data Solution™ (ISDS) Software. To ensure freedom from interferences, the subarray plots were examined and background correction points were set appropriately. The analyzed lines can be found in Table III. Table III. Results of the analysis

Element and Wavelength (nm)

Measure Spike Spike Concentration Concentration -1 mg kg -1 mg kg

Spike Recovery %

RSD on Three Replicates of Spike %

MDL -1 µg kg

Ag 328.068

2.34

2.44

104

1.36

3.4

Al 396.152

2.34

2.46

105

1.20

7.9

As 189.042

2.37

2.39

101

0.25

7.4

B 208.893

2.34

2.44

104

0.58

13

Ba 455.403

2.34

2.40

103

0.86

0.2

Ca 393.366

2.34

2.44

104

0.33

0.1

Cd 228.802

2.34

2.37

101

0.28

0.6

Cr 267.716

2.34

2.34

100

0.57

1.0

Cu 324.754

2.34

2.44

104

1.15

1.3

Fe 259.940

2.34

2.34

100

0.35

1.9

Hg 184.950

2.36

2.38

101

0.44

2.7

Mg 279.553

2.34

2.39

102

0.22

0.04

Mn 257.610

2.34

2.34

100

0.38

0.3

Mo 202.030

2.34

2.35

100

0.19

2.7

Na 589.592

2.34

2.43

104

1.43

10

Ni 221.647

2.34

2.30

98

0.32

1.6

P 178.284

2.34

2.36

101

0.19

11

Pb 220.353

2.34

2.27

97

0.12

7.6

Si 212.412

2.34

2.39

102

0.46

8.0

Sn 189.989

2.34

2.27

97

0.92

8.1

Ti 334.941

2.34

2.37

101

0.40

0.4

V 309.311

2.34

2.37

101

0.39

1.0

Zn 213.856

2.34

2.35

100

0.01

0.4

47

Determination of Trace Elements in Naphtha using ICP OES

Sponsor Report The results (Table III) show that all element recoveries fall within acceptable limits of ±5% of the true values. The relative standard deviation (RSD) of the three replicates of the spiked blank are below 1.5% for all elements, with the vast majority being below 0.5%. For the majority of analyzed elements, the method detection limits (MDL) are in the single digit µg kg-1 range or lower.

CONCLUSIONS The analysis of naphtha with the Thermo Scientific iCAP 7600 ICP-OES Radial is simplified by the addition of a Peltier cooled spray chamber set to -10 °C. This reduces the volatility of the solvent, which lowers the plasma loading, when the solvent is aspirated. The iCAP 7600 ICP-OES Radial can also detect sub single figure ppb concentrations of various elements within this complex and challenging matrix.

This sponsor report is the responsibility of Thermo Fisher Scientific.

REFERENCES 1. Leclercq, A.; Nonell, A.; Todolí Torró, J.L.; Bresson, C.; Vio, L.; Vercouter, T.; Chartier, F.; Anal.

Chim. Acta, 2015, 885, pp 33-56.

2. Leclercq, A.; Nonell, A.; Todolí Torró, J.L.; Bresson, C.; Vio, L.; Vercouter, T.; Chartier, F.; Anal.

Chim. Acta, 2015, 885, pp 57-91.

3. Brandão, G.P.; de Campos, R.C.; Luna, A.S.; de Castro, E.V.R.; Anal. Bioanal. Chem., 2006, 385, p 1562.

4. Agência Nacional do Petróleo, Ministério de Minas e Energia, 2008, http://www.anp.gov.br/

48

iCAP 7000 Series: Powerful, easy-to-use, solution for multi-element analysis The Thermo Scientific™ iCAP™ 7000 Plus Series ICP-OES provides low cost multi-element analysis for measuring trace elements in a diverse sample range. The innovative ICP-OES technology is driven by the Thermo Scientific™ Qtegra™ Intelligent Scientific Data Solution™ (ISDS) software and the Element Finder plug-in. The plug-in reduces method development time and removes the need for wavelength selection by the user.

Thermo Scientific iCAP 7000 Series

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14th Rio Symposium presented Innovations in Atomic Spectrometry The 14th Rio Symposium on Atomic Spectrometry was held between April 2 and 7, 2017, in Vitória city, Espírito Santo, Brazil, and brought together spectrometrists from all over the world.

The Rio Symposium on Atomic Spectrometry (Rio Symposium) occurs every two years and attracts approximately 300 participants. Many topics are discussed, such as atomic absorption spectrometry, optical emission spectrometry, plasma mass spectrometry, LIBS, X-ray fluorescence spectrometry, chemical vapor generation, speciation analysis, and sample preparation.

Dr. Adilson Curtius and Dr. Bernhard Welz founded the Rio Symposium in 1988, with the idea of giving scientists from Latin America, including students, an opportunity to join with renowned scientists from all parts of the world. The first two Symposia were realized in Rio de Janeiro, Brazil, and the next editions were realized in various Latin American countries such as Venezuela, Argentina, Mexico, and Chile. th The 14 Rio Symposium on Atomic Spectrometry provided a wide platform for academicians, professionals, fellow researchers, and postgraduate participants to interact and to share ideas, experience, and expertise in atomic spectrometry-related fields, and provided opportunities to discuss recent and new findings. In addition, the 2017 Rio Symposium created opportunities for networking and research collaboration among participants nationally, regionally, and internationally.

"Certainly, this event has great importance in the area of atomic spectrometry, because it brings together many researchers who are already researching at the highest level.

As the event takes place in Latin America, it is an opportunity for us to have contact with foreign researchers, including from Europe and the United States. In addition, subjects that are the state of the art in atomic spectrometry are discussed, so it really is an event of great scientific importance. The attending researchers themselves know that it is a moment of in-depth discussions on the subject, as several important issues are raised”, said Prof. Dr. Maria Tereza W. D. Carneiro Lima, from Prof. Dr. Maria Tereza W. D. Carneiro Lima the Federal University of Espírito Santo, and chair of the event. chair (first right) with members of the organizing committee. Photo: Rio Symposium

On April 2, a pre-symposium course was held on 'X-Ray Fluorescence Fundamentals: Theory and Practice', presented

by Pol De Pape. The opening lecture was given by Prof. Dr. Marco Aurélio Zezzi Arruda, from the Institute of Chemistry, State University of Campinas (Unicamp), with the theme 'An Exciting Journey through Light and Mass'.

Prof. Dr. Marco Aurélio Zezzi Arruda during the opening speech. Photo: Rio Symposium 50

Feature

The opening ceremony also offered a typical dance performance of Espírito Santo State performed by the Dance Company Andora Ufes. After the opening lecture, the event offered everyone a cocktail to facilitate interaction among the participants.

Dance Company Andora Ufes Photo: Rio Symposium

This edition of the event, like all previous ones, was given the added prestige of the attendance of great national and international names, like Prof. Dr. Bernhard Welz of the Federal University of Santa Catarina (UFSC), who addressed the topic 'Progress in the Determination of Halogens using HR-CS GF MAS and Direct Solid Sample Analysis', and Prof. Dr. Ewa Bulska of the University of Warsaw, Poland, who spoke on 'High Precision Direct Analysis of Strontium and Magnesium Isotope Ratio by Ion Chromatography/ Multicollector (ICP MS) using Wet and Dry Plasma Conditions'.

Throughout the event, there were the traditional oral presentations of scientific works, discussion of posters, and awards for the best posters. The awards were offered by Springer, Elsevier, and the Royal Society of Chemistry.

The participants also attended two lectures offered by the sponsors of the event, one from Thermo Scientific, titled 'All the Power, None of the Complexity: Introducing the New iCAP TQ', presented by Ana Rita Cristiano; and another from Agilent, titled 'Atomic Spectrometry: Innovation and Application Notes for All Markets', presented by Rodolfo Lorençatto.

According to Prof. Maria Tereza Lima, the sponsors are fundamental to the accomplishment of an event of this magnitude. “It's a very expensive event and, furthermore, it's international and we bring researchers from as far away as Europe”, she explained. For this purpose, an exhibition was held in parallel to the Symposium showing the latest developments in spectrometers and related accessories. Some of the companies present were Agilent Technologies, Thermo Fisher, Analítica, Milestone, Analytikjena, Rigku, Elemental Scientific, Applied Spectra, and Bio Solutions.

The event organizers were expecting a greater number of participants compared to previous events. However, that turned out not to be the case. “We attribute this smaller number, perhaps, to the financial crisis that Brazil is experiencing and the consequent lower support of universities. The research groups cannot afford all the expenses and only a smaller number of researchers can attend meetings”, said Prof. Maria Tereza Lima.

Meeting attendees interacting at ExpoCenter and social events. Photo: Lilian Freitas/Rio Symposium 51

Feature The traditional break in the middle of the event also happened in this edition and participants were able to visit some of the most beautiful beaches of Espírito Santo. In addition, there was a stop for lunch at a typical restaurant with the delicious moqueca capixaba.

Penha Convent: a historical icon of European colonization in Espírito Santo state.

Photo: Divulgação

A dinner was offered during the conference and was a good opportunity for participants to get to know each other and to build a network of friends from the atomic spectrometry field. At the 'bottle party', participants were invited to bring a bottle of a typical drink from their country. It was an evening with friends, eating finger food and enjoying a variety of drinks.

Traditional photo of all Rio Symposium attendees. Photo: Rio Symposium

52

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Releases Thermo Scientific iCAP 7000 Plus Series ICP-OES: Powerful, easy-to-use, solution for multi-element analysis

The iCAP 7000 Plus Series ICP-OES provides low cost multi-element analysis for measuring trace elements in a diverse sample range. The instrument combines advanced performance with high productivity and ease of use, resulting in consistently reliable data, whilst ensuring compliance with global regulations and standards.

The user-friendly sample introduction system with push-fit connections ensures rapid assembly and disassembly for cleaning and maintenance. Additional sample introduction components can be added to increase the speed of analysis or for the analysis of special sample types.

The high resolution optics enable effective interference separation. At 200 nm, the resolution is 7 pm enabling the simple analysis of complex line-rich samples without excessively elaborate deconvolution.

The low number of optical surfaces reduces reflective losses and maximizes light transmission from plasma to detector for superior detection limits. The echelle polychromator is thermostatically controlled to 0.1˚C to achieve long-term stability with recalibration typically only required every 24 hours.

The iCAP 7000 Plus Series ICP-OES features superior signal detection and large working dynamic range due to the unique CID. The CID enables complete access to the full spectrum between 166 and 847 nm in both radial and axial views, with the additional functionality to perform post-run integration of previously unquantified elements.

Analyze challenging samples with a self optimizing robust plasma delivered by the swing frequency RF generator. The innovative design of the iCAP 7000 Plus Series ICP-OES delivers powerful analytical performance and stability.

The innovative ICP-OES technology is driven by the Thermo Scientific™ Qtegra™ Intelligent Scientific Data Solution™ (ISDS) software and the Element Finder plug-in. The plug-in reduces method development time and removes the need for wavelength selection by the user. This delivers powerful, high performance and low-cost analysis for both high throughput routine and research laboratories.

The Thermo Scientific iCAP 7200 ICP-OES is a simple alternative to the Atomic Absorption technique and Microwave Plasma technology, providing a multi-element analysis solution for laboratories with increasing demands for sample throughput and lower detection limit capability.

The Thermo Scientific iCAP 7400 ICP-OES is ideal for QA/QC and contract laboratories requiring highest sensitivity from full wavelength coverage. The instrument achieves an advanced level of performance for a range of liquid applications with the minimum of user set-up and maintenance. The instrument offers laboratories broad analytical capabilities with stability, sensitivity and regulatory compliance.

The Thermo Scientific iCAP 7600 ICP-OES is the ideal solution for the most demanding analytical challenges. The instrument has the highest throughput, sensitivity and detection limits. Productivity is increased by the integrated sample loop which efficiently delivers the sample to the plasma. The iCAP 7600 ICP-OES maximizes scalability and advanced accessory connectivity to support expanding laboratory requirements.

54

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High-Pressure Ion Chromatography System Delivers New Levels of Simplicity and Flexibility Thermo Scientific Dionex Integrion High-Pressure Ion Chromatography (HPIC) system breaks new ground in productivity and efficiency for environmental, food safety, pharmaceutical and industrial/petrochemical laboratories Thermo Scientific Dionex Integrion High-Pressure Ion Chromatography (HPIC) system breaks new ground in productivity and efficiency for environmental, food safety, pharmaceutical and industrial/petrochemical laboratories (Photo: Business Wire).

“The new Dionex Integrion HPIC system delivers innovation from the inside out” The Thermo Scientific Dionex Integrion High-Pressure Ion Chromatography (HPIC) system, the newest addition to the Thermo Fisher Scientific ion chromatography portfolio, is intuitive and easy-to-use, and capable of addressing challenging laboratory workflows.

“The new Dionex Integrion HPIC system delivers innovation from the inside out,” said Evett Kruka, vice president and general manager, ion chromatography and sample preparation, Thermo Fisher. “With 40 years of expertise and innovation in ion chromatography, we have worked closely with our customers to develop a system on which they can rely to produce accurate and reproducible results, under a variety of conditions and circumstances. Whether scientists are using IC technology to analyze water, food and beverages, biofuels or pharmaceuticals, the Dionex Integrion HPIC system offers flexibility, ease-of-use and configurability to meet their evolving needs.”

The Dionex Integrion HPIC system delivers features previously available only on Thermo Scientific high-end systems, including high-pressure capability and optional electrochemical detection. With a simple, logical, flow-based plumbing layout and integrated performance features, including whole-system smart monitoring, the Dionex Integrion HPIC offers fast run times in a robust and reliable system. Additional features may include: · Easy-to-install IC PEEK Viper Fittings that enable easy operation and minimize peak dispersion and band broadening—ultimately improving chromatographic resolution. · Detachable tablet with local language support that allows the flexibility to access IC controls even while away from the instrument. · Consumables device monitor that regulates installation errors by logging and tracking both system and consumable performance—storing data in a secure, cloud server that improves preventative maintenance and maximizes uptime. · Thermally regulated detector compartment that provides extended life to consumables. · Thermo Scientific Dionex Chromeleon Chromatography Data System (CDS) software to streamline workflow from samples to results quickly and easily.

Also new to the Thermo Scientific IC portfolio is the Dionex Aquion IC system, which brings reliability in a compact platform and the simplified operation needed for routine IC analysis. Based on the company's reliable ICS-1100 platform, the system features electrolytic suppression for consistent performance and ease-of-use, an optional column heater for improved reproducibility and an optional vacuum degasser for improved baseline stability.

For more information on Thermo Scientific Dionex Integrion HPIC and Aquion visit: www.thermoscientific.com/chromatography.

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Br. J. Anal. Chem., 2017, 4 (15), pp 56-63

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Centro de Pesquisas e Análises Tecnológicas 40 Years dedicated to Quality Assurance of Fuels and Lubricants in Brazil Fábio da Silva Vinhado Centro de Pesquisas e Análises Tecnológicas (CPT) – Agência Nacional do Petróleo, Gás Natural e Biocombustíveis fvinhado@anp.gov.br Centro de Pesquisas e Análises Tecnológicas (CPT) is the research and technological analysis center of the National Agency of Petroleum, Natural Gas and Biofuels (ANP), which was established in Brasília, the Brazil federal capital, in 1997 and since then has contributed significantly to the development of the petroleum and biofuels industry in Brazil. Since the beginning of its activities, CPT has gained prominence as the lab. of quality control for the inspection of fuels in Brazil. Furthermore, after being incorporated into the ANP in 1998, the CPT has played the role of central laboratory for the Fuel Quality Monitoring Program (PMQC), by monitoring other laboratories, managing all technical improvements in the program and as a provider of proficiency testing. On research, CPT has developed some relevant studies of the ANP of interest, among which we can cite the evaluation of the characteristics for the orange dye to be added to anhydrous ethanol, development of a test method to determine methanol in gasoline and fuel ethanol, evaluation of absorption of water along the supply chain of biodiesel since production, etc. After its recent modernization, CPT seeks to expand its laboratory functions and thus, to consolidate itself as a reference laboratory in petroleum, its derivatives and biofuels.

CPT consists of a set of laboratories with instruments of the highest technology dedicated to studies and quality control of crude oil, its derivatives and biofuels. Located in Brasília, in an area of more than 3,000 m2, CPT started its activities in July 1977, with the name of CEPAT, the lab of the extinct National Council of Petroleum (CNP) that previously worked in Rio de Janeiro [1]. After the extinguishment of CNP, CEPAT was incorporated into the newly created National Fuel Department (DNC) at the beginning of 90s, when it had its assignments noticeably reduced. Established in 1998, ANP [2] incorporated the laboratory, which is linked to the Superintendence of Biofuels and Product Quality (SBQ), when its attributions were extended and it stood out once more in the national scenario of quality assurance of fuels in Brazil. Under ANP, the name has been kept, but the initials were changed from CEPAT to CPT. The laboratory in its various configurations had a prominent role in several actions that have helped to consolidate the industry of petroleum and ethanol in Brazil, among which the implantation of Proalcohol, inspection of fuels, implantation and maintenance of fuel quality monitoring system, register of products and advance of specifications of products. From 2013 to 2015, CPT underwent a significant renovation that resulted in a 23% increase in laboratory area and complete modernization of its installations, including segregation of areas by similarity of tests, modernization of exhaustion systems, effective access control, re-use of rainwater and waste disposal. Figure 1 shows a comparison of the external area of CPT, before and after renovation. Figure 2 shows one of the laboratories after modernization.

Figure 1: External area of CPT before and after renovation.

56

Releases

Figure 2: One of the laboratories of the CPT after modernization.

In 2017, CPT performs the following activities: a) physical-chemical tests in samples collected by inspections of ANP, in order to contribute to increasing efficiency in inspections and enhancement of combating fuel adulteration; b) tests in crude oil to define royalties, according to ANP Administrative Rule nº 206/2000; c) implementation of the Fuel Quality Monitoring Program (PMQC) in the Federal District and state of Tocantins; d) execution of the Lubricant Monitoring Program (PML), in which all samples of engine oils are analyzed by the CPT; e) research on crude oil, its derivatives and biofuels; f) providing proficiency testing for analyses of fuels, lubricants, biodiesel, solvent tracer and methanol; g) registration of lubricants and greases; h) support for the solvent tagging program; i) participating in national and international forums that give subsides for elaborating specifications. In the case of attending international standardization, it keeps ANP in line with the global vanguard in terms of biofuels and regulatory standards. Since 2011, workers of the CPT play a role of leadership in technical groups of ethanol and biodiesel in the International Organization for Standardization (ISO) [3]. j) supporting inspection actions of the ANP in agreement with other institutions, such as Public Prosecutor, Consumer Protection Program (Procon), National Institute of Metrology, Quality and Technology of Brazil (Inmetro), etc.

Quality monitoring programs According to the Law nº 9.478/1997, one of the attributions of the ANP is to protect the consumers on the quality of the derivatives of petroleum, natural gas and biofuels commercialized in the entire country.

In order to achieve this mission, in 1998 ANP created, through SBQ, the PMQC. Over the years, the program has grown in territorial scope and quantity of samples analyzed, already passing 2.5 million samples analyzed. In addition, it can state that PMQC stands out against similar programs from other countries [4], either by the amount of samples collected and analyzed or by the contribution to reduce indices of non-compliance of fuels over the years.

The PMQC follows the general indicators of quality of gasoline, ethanol and diesel marketed in Brazil in order to identify the existence of products in disagreement with the quality specifications determined by the ANP. In addition, to generate valuable data about the quality of main fuels marketed in the country, it constitutes an important tool for directing the inspection actions of the ANP [3]. Each month samples of gasoline, fuel ethanol and diesel are collected in gas stations chosen by lottery. Then, the samples are analyzed for various technical parameters in CPT and in the laboratories contracted by the ANP. Besides managing and executing the program in the Federal District and state of Tocantins, the CPT also manages a computerized system for management of laboratory data (LIMS) [5] in regard to specifications of products and tolerances of test methods, as well as technically supervising the performance of all laboratories in the program, through on-site visits, calibration of instruments and proficiency testing [6].

The year 2016 marks the consolidation of the return of laboratorial activities of the CPT after they were stopped due to the modernization; the center carried out tests in samples of gasoline, ethanol and diesel 57

Releases collected in more than 700 gas stations in the Federal District (DF) and Tocantins (TO) (Figure 3).

Figure 3: Tests carried out by CPT in 2016 in samples collected into the PMQC program in gas stations of DF and TO.

In parallel to the PMQC, the ANP keeps the Lubricant Monitoring Program (PML, since 2006) in order to systematically monitor the quality of engine oils marketed in Brazil and, in addition, to provide an important tool for directing inspection actions. The samples are collected in different points, such as gas stations, supermarkets, auto parts, distributors, etc. [7].

The same network of laboratories contracted for the PMQC is used in PML, but in this case, they just collect and send the samples to CPT that is the uniquely responsible for the analyses, including registration and physical chemical tests. On registration, the CPT team verifies the registration is active. Unlike fuels, where there is a defined quality specification, for lubricants, the quality is evaluated according to the data declared and approved at the moment of registration. It is necessary to emphasize that the data is confidential and only the CPT has the information. The following quality parameters have been evaluated in the PML: a) kinematic viscosity at 100 °C; b) kinematic viscosity at 40 °C; c) viscosity index; d) viscosity using the cold-cranking simulator (CCS); e) content of elements: calcium (Ca), magnesium (Mg), zinc (Zn) and phosphorus (P), whereby it is possible to evaluate the additivation of the engine oils; f) flash point; g) evaporation loss (NOACK)

Figure 4: Historical of non-compliances detected by the PML 58

Releases The labels of samples are not analyzed more since the ANP Resolution nº 22/2014 was published; all labels are verified at the moment of registration. In turn, inspections of the ANP continue verifying this topic. Figure 5 shows the laboratory of lubricants of the CPT.

Figure 5: Analysis of viscosity in the CPT laboratory of lubricants

Working together with the inspection area of the ANP Since the 70s, CEPAT has worked in conjunction with the area of fuel inspections, being the only governmental body to carry out monitoring of the fuel quality in Brazil [8]. Under DNC, CPT (formerly CEPAT) continued its mission to conduct tests on fuel samples collected by inspection actions. In 1996, evaluation of the results of these analyses, associated with data from the market, indicated that the quality of fuels in Brazil had problems. Then, in 1997, the DNC launched a mobile lab, a truck that circulated in some cities and that had active participation of the CEPAT technicians to carry out the quality tests.

Although, there were few trials, the need to create a mechanism capable of monitoring the quality of fuels frequently and in different places was detected, and this led to the creation of the PMQC, already under of the ANP.

Figure 6: Mobile lab of the DNC that worked in 1997.

In 2006 and 2007, ANP introduced another innovation in terms of inspections in gas stations in the cities of São Paulo and Rio de Janeiro, which consisted of a mobile lab equipped with a gas chromatograph to detect solvent tracers in gasoline, allowing for the identification of some cases of adulteration of gasoline by solvents of petroleum, such as toluene, 'aguarras', etc. Analyses were carried out by the chemists of the CPT that worked with the fiscals of the ANP [9]. The CPT always participated in inspection actions performed by the ANP (including its precursors CNP and DNC) and more recently in actions with contracting bodies such as Public Prosecutor, Procon, Inmetro, etc.

Figure 7: Mobile lab of the ANP in action in Rio de Janeiro in 2007 59

Releases Another activity consists of elaborating technical advices to support the sector responsible by the administrative processes in the ANP, which originated from inspections of the agency. The technical support of the CPT also includes training about tests, specifications and studies to improve the actions of the ANP in gas stations.

Proficiency testing Proficiency testing (or interlaboratory comparisons) consists of the organization, performance and evaluation of measurements or tests on the same or similar items by two or more laboratories in accordance with . predetermined conditions [10] Since 2001, the CPT organize proficiency testing for tests. This activity started with the aim to monitor the performance of the laboratories contracted by the PMQC to carry out tests in gasoline, fuel ethanol and diesel, and thus, led to the origin of the Inter-Laboratory Fuels Program (PIC).

After the introduction of the solvent tagging program, through ANP Administrative Rule nº 274/2001 and the subsequent introduction of marker detection analysis in PMQC contracts, in 2002, there was also a need to monitor the proficiency of laboratories contracted in the accomplishment of this test. This gave rise to the Inter-Laboratory Solvent Marking Program (PIM) of the ANP, whose first edition occurred in 2003 and where participants the laboratories contracted by the agency carry out this test and the marker supplier company.

Figure 8: Homogenizer system and samples prepared for a proficiency testing organized by the CPT

Another challenge appeared with the National Program for the Production and Use of Biodiesel (PNPB), instituted by the federal government in 2004, with the establishment of its mandatory in the Brazilian energy matrix. From the following year, it was possible to voluntarily add 2% of biodiesel to the mineral diesel [11] and from this, the addition became mandatory. In this context, in 2007, the CPT Inter-Laboratorial Program in Biodiesel (PIB) of the ANP was the first, and for many years the only, provider of proficiency testing for tests of biodiesel B-100 in Brazil. This program has the participation of more than 50 laboratories, which includes the producers, universities and service providers and already has one laboratory from abroad. In 2013, the CPT implemented the Inter-Laboratory Program for Methanol (PIME) of the ANP to evaluate the performance of the laboratories contracted in the PMQC to carry out the test of determining methanol in gasoline and fuel ethanol according to the standard ABNT NBR 16041 [12].

On the basis of the experience gained by the CPT over the years, in 2016 it was possible to create specific proficiency testing for the market of lubricants. This occurred with the First Edition of InterLaboratory Comparison Program in Lubricants (PIL) of the ANP that had 33 participating laboratories, most of them from the producers of engine oil.

It is important to point out that all proficiency testing (or inter-laboratory programs) organized by the CPT use the consensus value with obtaining a (Z)-score as the performance indicator of each participating laboratory [13]. The exception was in 2011, when in an ANP/Inmetro partnership, a proficiency testing for biofuels (fuel ethanol and biodiesel) was provided using an assigned value [14]. This edition counted on the participation of more than 40 laboratories.

60

Releases Research and development Through the years, the CPT has developed several studies in order to give technical information to enhance specifications of quality and test methods for using in the monitoring programs and inspections of the ANP. Table I summarizes some studies developed in the CPT that helped to bring practical solutions for the industry of petroleum, its derivatives and biofuels.

P roduct

Table I: Mains studies carried out by the CPT R esearch C ontext

R esults

F uel etha nol

C P T conducted stud ies th a t resulted in th e first specificatio ns for the q uality of ethan ol in the w orld (70s and 80s).

A t th e b eginn ing of P roa lcoho l, the C N P create d a w ork ing gro up to e lab orate on th e specifications of qua lity for the ne w fuel (ethan ol), w hich w as atten ded b y th e representa tives of the autom obile industry, sug ar energ y ind ustry a nd environm ental ag encies, under the co ordination of th e C P T (form er C E P A T ) [1].

P ub licatio n of the R eso luçã o C N P 8 /19 79. S u bsequ ently, the gro up id entified proble m s of corrosion tha t led to im provem ents in regu latio n , w ith the pub lica tio n of th e R esoluçã o C N P 1 0/1 986 a nd later resu lte d in th e A dm inistrative R u les C N P C epat 42/198 9 a nd M infra 774/199 0 [1].

F uel etha nol

S tud ies to create the specificatio n of qua lity to th e ne w d ye to be a dde d to anh ydro us eth ano l (20 05).

D ue to tax m atters, a com m on practice consiste d of adding w ater to an h yd ro us etha nol m ixed w ith gaso lin e, in ord er to prod uce gaso lin e C ; th is caused prob lem s to consum er. T hen, A N P decid ed to m ark anh ydro us etha nol to differentiate it from the fuel eth ano l (colorless).

Incorporation of a specificatio n ta ble for the d ye in a ne w resolution of fuel etha nol R eso lução A N P 36/2 005.

D iese l

D evelo pm ent of a test m ethod to de tect p ossible contam ination of d iesel b y veg eta ble oil in n ature (2008).

A t th e b eginn ing of the m andatory a dditio n of bio diese l in d iese l, there w as a concern a bo ut irre gular add itions of the nontransesterified oil to th e diese l. T hen, the C P T develope d a test m ethod b y gas chrom atograph y to detect this p ossible a dd itio n.

C arrying o ut a na lyses on severa l P M Q C sam ples, m ainly th at w ith biod iesel content out of specificatio n. A paper w as pu blished describing the m ethod develope d [1 5].

D iese l

E valu ation of m ethodo lo gie s to de term ine biodiesel content in m ineral d iese l.

A t th e b eginn ing of the m andatory a dditio n of bio diese l in d iese l, the A N P need ed to incorpora te a standard to this determ ination in a ll lab oratories of the P M Q C .

T hen, the C P T eva lu ate d th e test m ethods availab le from A B N T , E N an d A S T M and decid ed o n th e E urop ean standard, since it re quires only m onovariate calibratio n.

T he standard E N 140 78 [1 6] w as incorp orate d in a ll contracts of the P M Q C .

M ark ing of solvents

E valu ation of test m ethods for the solvent tag ging program .

T he C P T evaluated m an y test m ethods from com panies that lo ok to the A N P to sh o w th eir techno log ies for m ark ing solvents in ord er to com ply w ith the sp ecific le gislation of the a genc y.

R egu lation of the techn ical requirem ent for registratio n of m ark er vendor, accordin g to A rt. 12 º of the R esolução A N P 13/200 9.

61

Releases Since its establishment, the CPT has accomplished the evolution of the petroleum, oil products and biofuels sector in Brazil, especially in the advances in product specifications and in the implementation and development of the PMQC. Under this program, CPT has always acted as a central laboratory, with attributes that include the elaboration of tolerances for tests, technical visits and performance evaluation of contracted laboratories.

In addition, CPT's partnership with the ANP's inspection area is historic and, by 2017, this integration aims to obtain increasingly accurate and advanced instruments and test for field activities.

The development of research on quality control of fuels and lubricants is another trademark of the CPT, including work of international relevance. Finally, it should be noted that the advances made in recent years have been possible thanks to the commitment and active participation of its own technical staff, made up of several masters and doctors who are part of the CPT framework.

Acknowledgments I am grateful to Agência Nacional do Petróleo, Gas Natural e Biocombustíveis for all the support to maintain and development the CPT along the years.

I am also grateful to Edmilson Raldenes for giving me some important information and Figure 6, and to Vinicius Skrobot and Felipe Feitosa for the graphics.

References

1. Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP). CPT 30 anos, publicação comemorativa. 2008.

2. Law No. 9478 of August 6, 1997. Presidency of the Republic of Brazil.

3. Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP). Petróleo e Estado. 2015.

4. Araújo, R.M., Monteiro, C.Z.A. e Lima, A.S. A Qualidade dos Combustíveis no Brasil. Em: Combustíveis no Brasil: desafios e perspectivas. Rio de Janeiro, Synergia: Centro de Estudos de Energia e Desenvolvimento (CEEND), 2012.

5. Laboratory Information Management System.

6. Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP). Boletim de Monitoramento da Qualidade dos Combustíveis. Rio de Janeiro: novembro de 2016a.

7. Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP). Boletim do Programa de Monitoramento de Lubrificantes. Rio de Janeiro: novembro de 2016b.

8. Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP). O Programa de Monitoramento da Qualidade dos Combustíveis – PMQC, séries temáticas nº 5, Rio de Janeiro, 2012.

9. http://g1.globo.com/Noticias/SaoPaulo/0,,MUL12931-5605,00LABORATORIO+MOVEL+INTERDITA+POSTOS+EM+SP.html / http://atarde.uol.com.br/brasil/noticias/1156351-anp-fiscaliza-postos-de-gasolina-na-saida-para-oferiadao.

10. ISO 17043 – Conformity assessment – General requirements for proficiency testing 11. Law nº 11097, of January 13, 2005. Presidency of the Republic of Brazil.

12. ABNT NBR 16041 - Etanol combustível - Determinação dos teores de metanol e etanol por cromatografia gasosa.

13. ISO 13528 – Statistical methods for use in proficiency testing by inter-laboratory comparisons.

14. Gonçalves, M.A. et al. Química Nova, 2013 36 (3), p 393.

15. Vinhado, F.S.; Oliveira, B.N.L.B.; Brandão, L.F.P. Br. J. Anal. Chem., 2013, 3 (9), pp 388-392.

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Releases

4 (15), pp 56-63

Releases

‫  و‬EN 14078 – Liquid petroleum products - Determination of fatty acid methyl ester (FAME) content in 16. middle distillates. Infrared spectrometry method.

2. Coelho, M.C.S.; Valente, V.S.B.; Teixeira, R.M.; Viscardi, S. LC. 5º Congresso da Rede Brasileira de 17.

Tecnologia de Biodiesel, ID 1097. Salvador: 2012.

3. Filho, W.P.O.; Dupim, M.; Saint Pierre, T.D.; Vale, F.; Temistocles, J.C.T. 13th Rio Symposium.

18.

2014.

19.

4. Quintino, M.; Filho, W.O.; Vinhado, F.; Santos, W.; Dutra, R.; Oliveira, P., Costa, P. Soares, I. Química Nova, in press.

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Events 2017 9-14 July 46th IUPAC World Chemistry Congress (IUPAC-2017) & 40th Annual Meeting of the Brazilian Chemical Society WTC Sheraton, São Paulo, SP, Brazil http://www.iupac2017.org 31 July - 5 August IMEKO TC1-TC7-TC13 Joint Symposium Rio Othon Palace, Rio de Janeiro, RJ, Brazil http://imeko-tc7-rio.org.br/ 28 August - 1 September XIX Euroanalysis 2017 - Europe's Analytical Chemistry Meeting Stockholm, Sweden http://www.euroanalysis2017.se 3-6 September II Workshop of Inorganic Mass Spectrometry (II-WIMS) Institute of Geosciences, University of São Paulo (USP), SP, BR http://wims.igc.usp.br 24-27 September 131st AOAC Annual Meeting Atlanta, GA, USA http://www.aoac.org 26-28 September 14th Analitica Latin America & 5th Analitica Latin America Congress São Paulo Expo, São Paulo, SP, Brazil http://analiticanet.com.br/ 9-12 October 9th Eurachem International Workshop on Proficiency Testing in Analytical Chemistry, Microbiology and Laboratory Medicin - Current Practice and Future Directions Portoroz, Slovenia http://www.eurachempt2017.eu 7-10 November RAFA 2017 - 8th International Symposium on Recent Advances in Food Analysis Prague, Czech Republic http://www.rafa2017.eu 3-8 December 3rd BrMASS School of Mass Spectrometry SERHS Hotel, Natal, RN, Brazil http://www.escola.brmass.com 10-13 December 5th Brazilian Meeting on Chemical Speciation Águas de Lindóia, SP, Brazil http://www.unesp.br/portal#!/cea/home/espeqbrasil2017 64

Br. J. Anal. Chem., 2017, 4 (15), pp 65-66

Notices of Books Advances of Basic Science for Second Generation Bioethanol from Sugarcane Marcos S. Buckeridge and Amanda P. De Souza, Editors March 2017, Springer This book focuses on the basic science recently produced in Brazil for the improvement of sugarcane as a bioenergy crop and as a raw material for 2nd generation bioethanol production. It reports achievements that have been advancing the science of cell walls, enzymes, genetics, and sustainability related to sugarcane technologies and give continuity to the research reported in the “Routes to Cellulosic Ethanol”. Read more…

Advances in Sugarcane Biorefinery Anuj Chandel and Marcos Henrique Luciano Silveira, Editors November 2017, Elsevier This book compiles the basic and applied information covering cane and biomass processing for sugar and ethanol production, as well as by-products utilization for improving the economy of sugarcane biorefineries. In this unique collection of 14 chapters, specialists in their field provide critical insights into several topics, review the current research, and discuss future progress in this research area. Read more…

Biomass Volume Estimation and Valorization for Energy Jaya Shankar Tumuluru, Editor February 2017, InTech, Open access Publisher This book is the outcome of contributions by many experts in the field from different disciplines, various backgrounds, and diverse expertise. It provides information on biomass volume calculation methods and biomass valorization for energy production.

The chapters presented in this book include original research and review articles.

Chapter 11 presents the biomass compositional analysis for conversion to renewable fuels and chemicals, by C. Luke Williams, Rachel M. Emerson and Jaya Shankar Tumuluru. Read more…

The Science and Technology of Unconventional Oils Maria Magdalena Ramirez-Corredores, Author May 2017, Academic Press This book intends to report the collective physical and chemical knowledge of unconventional oils (heavy, extra-heavy, sour/acid, and shale oil) and the issues associated with their refining for the production of transportation fuels. It will focus on the discussion of the scientific results and technology activities of the refining of unconventional oils. Read more…

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Books Charged Aerosol Detection for Liquid Chromatography and Related Separation Techniques Paul H. Gamache, Editor May 2017, Wiley The first book devoted exclusively to a highly popular, relatively new detection technique. This book presents a comprehensive review of Charged aerosol detection (CAD) theory, describes its advantages and limitations, and offers extremely well-informed recommendations for its practical use. Using numerous real-world examples based on contributors' professional experiences, it provides priceless insights into the actual and potential applications of CAD across a wide range of industries. Read more…

Analysis of Samples of Clinical and Alimentary Interest with Paper-based Devices Nominated as an outstanding Ph.D. thesis by the University of Campinas, Brazil Emilia Witkowska Nery, Author August 2016, Springer This book presents two main sets of paper-based analytical systems. The first set is a platform for the analysis of glucose, cholesterol and uric acid in biological samples, and the second set is a cutting-edge electronic tongue system for the analysis of beverages (mineral water, beer, wine). This thesis also provides an extensive review of 33 methods of enzyme immobilization on paper which have been evaluated to enhance the storage stability of the proposed system for biomarker detection. Read more…

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Br. J. Anal. Chem., 2017, 4 (15), pp 67-69

Author's Guidelines

Download

The Brazilian Journal of Analytical Chemistry (BrJAC) is a peer-reviewed scientific journal intended for professionals and institutions acting mainly in all branches of Analytical Chemistry. BrJAC is an open access journal which does not charge authors an article processing fee.

Scope BrJAC is dedicated to professionals involved in science, technology and innovation projects in the area of analytical chemistry at universities, research centers and in industry.

About this journal BrJAC publishes original, unpublished scientific articles and technical notes that are peer reviewed in the double-blind way. In addition, it publishes reviews, interviews, points of view, letters, sponsor reports, and features related to analytical chemistry.

BrJAC's review process begins with an initial screening of the manuscripts by the editor-in-chief, who evaluates the adequacy of the study to the journal scope. Manuscripts accepted in this screening are then forwarded to at least two referees indicated by the editors. As evaluation criteria, the referees will employ originality, scientific quality and contribution to knowledge in the field of Analytical Chemistry, the theoretical foundation and bibliography, the presentation of relevant and consistent results, compliance to the journal's guidelines, and the clarity of writing and presentation.

Brief description of the BrJAC sections · Articles: Full descriptions of an original research finding in Analytical Chemistry. Manuscripts submitted for publication as articles, either from universities, research centers, industry or any other public or private institution, cannot have been previously published or be currently submitted for publication in another journal. Articles undergo double-blind full peer review. · Reviews: Articles on well-established subjects, including a critical analysis of the bibliographic references and conclusions. Manuscripts submitted for publication as reviews must be original and unpublished, and undergo double-blind full peer review. · Technical Notes: Concise descriptions of a development in analytical method, new technique, procedure or equipment falling within the scope of BrJAC. Technical notes also undergo double-blind full peer review.

The title of the manuscript submitted for technical note must be preceded by the words "Technical note". · Sponsor Reports: Concise descriptions of technical studies not submitted for review by referees. Sponsor responsibility documents. · Letters: Discussions, comments, suggestions on issues related to Analytical Chemistry, and consultations to authors. Letters are welcome and will be published at the discretion of the editor-in-chief. · Points of view: The expression of a personal opinion on some relevant subject in Analytical Chemistry. · Interviews: Renowned chemist researchers are invited to talk with BrJAC about their expertise and experience in Analytical Chemistry. · Features: A feature article gives to the reader a more in-depth view of a topic, a person or opinion of acknowledged interest for Analytical Chemistry.

Manuscript preparation (download a template on the BrJAC website) The manuscript submitted to BrJAC must be written in English and should be as clear and succinct as possible. It must include a title, an abstract, a graphical abstract, keywords, and the following sections: Introduction, Methods, Results and Discussion, Conclusion, and References. Because the manuscripts are subjected to double-blind review, they must NOT contain the authors' names, affiliations, or acknowledgments. The manuscript must be typed in Arial font size 11 pt., and the lines numbered consecutively and double-spaced throughout the text, except in the figure captions, titles of tables and references.

67

Author's Guidelines The manuscript title should be short, clear and succinct, and a subtitle may be used, if needed. The abstract should include the objective of the study, essential information about the methods, the main results and conclusions. Then, three to five keywords must be indicated. The section titles should be typed in bold and subsections in italics. Graphics and tables must be numbered according to their citation in the text, and should appear close to the discussion about them. For figures use Arabic numbers, and for tables use Roman numbers. The captions for the figures must appear below the graphic; for the tables, above. The same result should not be presented by more than one illustration. For figures, graphs, diagrams, tables, etc. identical to others previously published in the literature, the author must ask for permission for publication from the company or scientific society holding the copyrights, and send this permission to the BrJAC editor-in-chief with the final version of the manuscript.

The chemical nomenclature should conform to the rules of the International Union of Pure and Applied Chemistry (IUPAC) and Chemical Abstracts Service. It is recommended that, whenever possible, authors follow the International System of Units, the International Vocabulary of Metrology (VIM) and the NIST General Table of Units of Measurement. Abbreviations are not recommended except those recognized by the International Bureau of Weights and Measures or those recorded and established in scientific publications. If the abbreviations are numerous and relevant, place their definitions in a separate section (Glossary).

The manuscript must include only the consulted references, numbered according to their citation in the text, with numbers in square brackets. It is not recommended to mention several references with identical statements - select the author who demonstrated them. It is recommended that references older than 5 (five) years be avoided, except in relevant cases. Include references that are accessible to readers.

References should be thoroughly checked for errors before submission.

Examples of reference formatting Journals 1. Cochran, R.E.; Dongari, N.; Jeong, H.; Beránek, J.; Haddadi, S.; Shipp, J.; Kubátová, A. Anal.

Chim. Acta, 2012, 740, pp 93-103.

The titles of journals must be abbreviated as defined by the Chemical Abstracts Service Source Index (CASSI). If a paper does not have a full reference, please provide its DOI, if available, or its Chemical Abstracts reference information.

Electronic journals 2. Natarajan, S.; Kempegowda, B.K. LCGC North America, 2015, 33 (9), pp 718-726. Available from: http://www.chromatographyonline.com/analyzing-trace-levels-carbontetrachloride-drug-substanceheadspace-gc-flame-ionization-detection [Accessed 10 November 2015].

Books 3. Burgot, J.-L. Ionic Equilibria in Analytical Chemistry. Springer Science & Business Media, New York, 2012, Chapter 11, p 181.

4. Griffiths, W.J.; Ogundare, M.; Meljon, A.; Wang, Y. Mass Spectrometry for Steroid Analysis. In: Mike, S.L. (Ed.). Mass Spectrometry Handbook, v. 7 of Wiley Series on Pharmaceutical Science and Biotechnology: Practices, Applications and Methods. John Wiley & Sons, Hoboken, N.J., 2012, pp 297-338.

Standard methods 5. International Organization for Standardization. ISO 26603. Plastics — Aromatic isocyanates for use in the production of polyurethanes — Determination of total chlorine. Geneva, CH: ISO, 2017.

Master’s and doctoral theses or other academic literature 6. Ek, P. New methods for sensitive analysis with nanoelectrospray ionization mass spectrometry.

Doctoral thesis, 2010, School of Chemical Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.

Patents 7. Trygve, R.; Perelman, G. US 9053915 B2, June 9 2015, Agilent Technologies Inc., Santa Clara, CA, US. 68

Author's Guidelines Web pages 8. http://www.chromedia.org/chromedia [Accessed 21 June 2015].

Unpublished source 9. Mendes, B.; Silva, P.; Pereira, J.; Silva, L.C.; Câmara, J.S. Poster presented at: 36th International Symposium on Capillary Chromatography, 2012, Riva del Garda, Trento, IT. 10. Author, A.A. J. Braz. Chem. Soc., in press.

11. Author, B.B., 2015, submitted for publication.

12. Author, C.C., 2011, unpublished manuscript.

Note: Unpublished results may be mentioned only with express authorization of the author(s). Personal communications can be accepted exceptionally.

Manuscript submission Two different PDF files, as described below, must be sent online through the website www.brjac.com.br I. A cover letter addressed to the editor-in-chief with the full manuscript title, the full names of the authors and their affiliations, the complete contact information of the corresponding author, including the ORCID iD, and the manuscript abstract. This letter must present why the manuscript is appropriate for publication in BrJAC, and contain a statement that the article has not been previously published and is not under consideration for publication elsewhere. The corresponding author must declare on behalf of all the authors of the manuscript any financial conflicts of interest or lack thereof. This statement should include all potential sources of bias such as affiliations, funding sources and financial or management relationships which may constitute a conflict of interest. When the manuscript belongs to more than one author, the corresponding author must also declare that all authors agree with publication in BrJAC. II.The manuscript file that must NOT mention the names of the authors or the place where the work was performed, but must include the title, abstract, keywords, and all sections of the work, including tables and figures, but excluding acknowledgments that will be included in the final paper upon completion of the review process.

A sponsor report should be sent as a Word file attached to a message to the email brjac@brjac.com.br Revised manuscript submission Based on the comments and suggestions of the reviewers and editors a revision of the manuscript may be requested to the authors. The revised manuscript submitted by the authors must contain the changes made in the manuscript clearly highlighted. A letter without any author's information must also be sent with each reviewer's comment items and a response to each item.

Copyright When submitting their manuscript for publication, the authors agree that the copyright will become the property of the Brazilian Journal of Analytical Chemistry, if and when accepted for publication. The copyright comprises exclusive rights of reproduction and distribution of the articles, including reprints, photographic reproductions, microfilms or any other reproductions similar in nature, including translations.

Final Considerations Whatever the nature of the submitted manuscript, it must be original in terms of methodology, information, interpretation or criticism.

As to the contents of published articles, the sole responsibility belongs to the authors, and Br. J. Anal.

Chem. and its editors, editorial board, employees and collaborators are fully exempt from any responsibility for the data, opinions or unfounded statements.

BrJAC reserves the right to make, whenever necessary, small alterations to the manuscripts in order to adapt them to the journal rules or make them clearer in style, while respecting the original contents. The article will be sent to the authors for approval prior to publication.

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April - June 2017 Volume 4 Number 15