By James Shurko, PharmD, PhD and Niti Vance, PhD

More Than a Test for Illicit Drugs:

Utilization of Urine Drug Tests to Manage Patients

By James Shurko, PharmD, PhD and Niti Vanee, PhD

Clinicians are faced with a number of challenges on a daily basis. When treating patients, they are tasked with evaluating medication safety and effectiveness, assessing medication adherence and identifying medication diversion. In some cases, the effectiveness of medications can easily be observed by simple physical assessment e.g., ACE inhibitors and blood pressure. In other instances, however, treatment relies heavily on patient response to subjective rating scales. Treatment with analgesics and anti-depressants are prime examples.

Medication non-adherence is a common problem with 20-30% of prescriptions remaining unfilled and 50% of medications used for the treatment of chronic diseases being taken in a manner other than prescribed. Further, healthcare costs due to nonadherence have been reported as approximately $20,000 per patient per year and upwards of $300 billion annually.1,2 Finally, drug diversion, characterized by the sale, loss or theft of medication has been reported in 45% of patients and is common in many medications including opioids and benzodiazepines.3 These challenges pose problems for clinicians when creating or modifying a current drug regimen since the medications are not being utilized as assumed. Urine drug testing through antibody-based screens and chromatography-based confirmation offer a way to assess medication utilization and therefore serve as a tool to mitigate these challenges.

The concept of medication monitoring is well established. Digoxin levels, prothrombin times, vancomycin troughs and non-protein bound phenytoin levels represent a mere fraction of the instances in which medications are monitored. Notably, these practices all require blood tests and can be invasive, especially in the outpatient setting where drawing from an IV is rarely an option. Herein lies the value of urine drug testing (UDT). While UDT is commonly employed in the work, sporting or legal arenas, these tests can be implemented by clinicians seeking to gain insight into medication effectiveness and evaluate medication utilization in scenarios when blood testing is not an ideal option or commonly practiced. Comparatively, UDT are relatively easy to implement and non-invasive. For example, urine drug screens (UDS) can be performed as a point of care test by using urine testing cups. These tests work through immunochromatography in which antigen linked compounds are separated by capillary beds and then detected through binding with corresponding antibodies.4 Positive tests can then be sent for further analysis as a “reflex” test for confirmation. Alternatively, urine cups or tubes can be sent directly to toxicology labs to identify specific compounds. These compounds are generally identified in a two-stage manner. First, a screening method, such as an antibody/antigen-based immunoassay is conducted to detect drugs or metabolites within a panel of compounds. Second, a confirmatory test is performed. Confirmatory tests are performed to account for limitations associated with UDS. Despite incorporating sample validity tests to identify adulteration such as urine creatinine, nitrites, pH and specific gravity, UDS can still be affected by masking agents leading to a negative result. Additionally, UDS are prone to false positive results due to cross-reactivity. For example, ibuprofen has been shown to crossreact with and lead to false positive tests for barbiturates and THC.5

Lastly, immunoassay-based screens primarily offer qualitative positive or negative results, but generally do not provide specific drug levels.

While drug screens rely on immunoassay, confirmation utilizes a more sensitive and specific chromatography-based method. With high performance liquid chromatography-mass spectrometry (LCMS) for example, samples are mixed with a solution (mobile phase) and under high pressure sent through a small column (stationary phase) containing different functional groups. The affinity of a compound to the mobile phase compared to the stationary phase determines how long it stays in the column (retention time). This technology is combined with mass spectrometry where compounds are ionized, fragmented and detected based on a resulting mass to charge ratio. The result is a test that can provide the clinician with a wealth of information since drug and metabolite concentrations can be evaluated in a quantitative manner.

When drug diversion is suspected, a negative UDT may support the clinician’s hypothesis. When assessing medication adherence, a confirmatory test can not only inform the clinician of whether or not the drug was ingested through a positive or negative result, but also provide insight into when the drug was last taken. For example, a scenario where a drug is not detected but its metabolite is present is suggestive of a patient with inconsistent adherence. In this case, the drug may have been ingested several days prior but was cleared to a point that it remained undetected. Further, simply conducting UDT has been shown to improve adherence theoretically as a result of a more thorough follow-up.6

Finally, these tests can provide insight into lack of efficacy. Oral medications are subject to the “first pass effect” in which drugs cross the gastrointestinal mucosa, enter the hepatic portal system and become metabolized by the liver before entering the circulatory system. High levels of a drug with low levels of its metabolite may suggest that the drug is being poorly metabolized, for example. Whether the parent drug exerts activity or has to be metabolized to an active compound will then determine the effect on a patient. Codeine, for example, is commonly thought to exert its analgesic effect largely through its conversion to morphine.7 A patient with a UDT showing high levels of codeine in the absence of morphine may experience less analgesia than a patient with both compounds present. Additionally, if low levels of codeine and high levels of morphine are detected, this patient would likely be metabolizing codeine quickly and the high levels of morphine could lead to adverse drug effects.

Overall UDT gives clinicians insight into the utilization and effects of a given drug regimen and provides them with a tool to make more informed decisions when managing patients. When considering using a UDT, be sure to verify whether or not the cost will be covered by the patient’s insurance.

For more information on lab testing services, please contact iGenomeDx Inc. at (210) 257-6973 or visit their website at https://www.igenomedx.com/contact-us.

References 1. Viswanathan, M., Golin, C. E., Jones, C. D., Ashok, M., Blalock,

S. J., Wines, R. C. M., Coker-Schwimmer, E. J. L., Rosen, D. L.,

Sista, P., & Lohr, K. N. (2012). Interventions to improve adherence to self-administered medications for chronic diseases in the

United States. Annals of Internal Medicine, 157(11), 785. https://doi.org/10.7326/0003-4819-157-11-201212040-00538 2. Cutler RL, Fernandez-Llimos F, Frommer M, et al Economic impact of medication non-adherence by disease groups: a systematic reviewBMJ Open 2018;8:e016982. doi: 10.1136/bmjopen-2017016982 3. Walker, DNP, M. J., & Webster, MD, L. R. (2012). Risk factors for drug diversion in a pain clinic patient population. Journal of Opioid Management, 8(6), 351–362. https://doi.org/10.5055/jom.2012.0135 4. Blurapids Drug Test Cup insert - tanner scientific. (n.d.). Retrieved

March 18, 2022, from https://tannerscientific.com/manuals/Blu-

Rapids-Drug-Test-Cup-Insert.pdf 5. Alec Saitman, Hyung-Doo Park, Robert L. Fitzgerald, False-Positive Interferences of Common Urine Drug Screen Immunoassays:

A Review, Journal of Analytical Toxicology, Volume 38, Issue 7,

September 2014, Pages 387–396, doi.org/10.1093/jat/bku075 6. Yee DA, Hughes MM, Guo AY, Barakat NH, Tse SA, Ma JD, Best

BM, Atayee RS. Observation of improved adherence with frequent urine drug testing in patients with pain. J Opioid Manag. 2014

Mar-Apr;10(2):111-8. doi: 10.5055/jom.2014.0200. PMID: 24715666. 7. Gasche, Y., Daali, Y., Fathi, M., Chiappe, A., Cottini, S., Dayer, P., & Desmeules, J. (2004). Codeine intoxication associated with ultrarapid CYP2D6 metabolism. New England Journal of Medicine, 351(27), 2827–2831. https://doi.org/10.1056 /nejmoa041888

James Shurko, PharmD, PhD is a laboratory scientist at iGenomeDx Inc.

Niti Vanee, PhD is the CEO of iGenomeDx Inc. iGenomeDx is a gold level Circle of Friends sponsor of the Bexar County Medical Society.