Pharmaceutical Chemistry Review Volume 1 2015 http://www.bacpl.org/J/pcr
Development and Validation of a Non‐ Aqueous Titrimetric Assay for the Determination of Pregabalin in Bulk Drug Luciana Petrone, Mariela Baldut, Silvina L. Bonafede, Laura D. Simionato, Adriana I. Segall Cátedra de Calidad de Medicamentos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junín 956, 1113 Buenos Aires, Argentina. Abstract New, accurate, sensitive and economical non‐aqueous volumetric method for the determination of pregabalin in raw material has been developed. The titrimetric method involves the reaction of perchloric acid with pregabalin and crystal violet was used as indicator to detect the end of the titration. The method was validated by following the analytical performance parameters suggested by the International Conference on Harmonization (ICH). The calibration curve was linear from 80 to 120 % with r = 0.9994. Statistical treatment of the experimental results indicated that the method is precise and accurate. The proposed method can be used for quality control assay of pregabalin in bulk drug. Keywords Pregabalin; Non‐Aqueous Titrimetry; Assay
Introduction Pregabalin (Fig 1) is (S)‐3‐(Aminomethyl)‐5‐methylhexanoic acid. It has been shown to be clinically effective and is approved for the treatment of postherpetic neuralgia, fibromyalgia, neuropathic pain associated with diabetic peripheral neuropathy, neuropathic pain associated with spinal cord injury, and as adjunctive therapy for adult patients with partial onset seizures in the United States. In Europe, pregabalin is approved for the treatment of central and peripheral neuropathic pain, generalized anxiety disorder, and also as adjunctive therapy for adult patients with partial onset seizures with or without secondary generalization. Pregabalin binds to the α2δ1 and α2δ2 subunits of voltage‐sensitive calcium channels with high affinity. Mutation of the α2δ1 subunit blocked pregabalin effects in neuro‐pathic pain and anxiety‐related assays; however, mutation of the α2δ2 subunit had no effect on anxiolytic activity [1]. The usual doses are capsules or tablets containing 25, 50, 75, 150 and 300 mg.
FIGURE 1 PREGABALIN
Pregabalin has been determined by spectrophotometric methods introducing a chromophoric group, in pure drug [2‐5] and with other drugs [6‐7], electrophoresis capilar [8‐9], HPTLC [10] and gas chromatography [11]. A literature survey revealed some high‐performance liquid chromatographic methods for the quantitation of pregabalin in biological fluids [12‐16] and in pharmaceutical products [17‐22] and using UPLC [23‐24]. Due to the need for an absolute analytical technique for pregabalin, we have developed this volumetric technique. The non‐aqueous titrations have become of considerable importance in pharmaceutical analysis because it is very simple and easily adoptable to determine active pharmaceutical ingredients, especially in the developing countries where modern and expensive instruments are not available.
Author to whom correspondence should be addressed: e-mail: asegall@ffyb.uba.ar.
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