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Scripta Scientifica Pharmaceutica

Possible reasons for the occurrence of false-negative results in urine drug screening

Stanila Stoeva

Abstract

Introduction: Immunoassay screening of urine samples play a central role in the monitoring and fight against ever-increasing drug abuse. Thus, the aim of the present work was to clarify the reasons for deliberately or unintentionally causing of false-negative screening results.

Materials and Methods: For the purpose of the study, an analysis of Google Scholar, PubMed, and Science Direct databases was conducted.

Results:  The exact number of false-negative results in the analytical practice cannot be precisely determined because of the impossible confirmation of each screening test. In this regard, the screening of drug abuse appears to be a huge challenge these days due to multiple reasons. On the one hand, it is necessary to take into account the physicochemical properties of sometimes an unknown analyte, as well as the physiological characteristics of each individual. On the other hand, the test antibodies available to date do not have the necessary specificity for absolutely all drugs, especially designer ones. At the same time, there is an unlimited access to information and products supporting the manipulation of urine samples, respectively the achievement of false-negative results. In response, analytical chemistry offers a variety of methods to address the problem of filtering out abusers.

Conclusion: Because of their high throughput and low cost, immunoassay techniques continue to be a cornerstone of drug screening, whether for clinical or criminological purposes. However, the risk of false-negative results requires efforts to improve their specificity in parallel with the implementation of countermeasures against the manipulation of the biological samples.


Keywords

immunoassay; false-negative; drugs; adulteration; urine sample

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References

UNODC, World Drug Report 2022 (United Nations publication). Booklet 2 - Global overview of drug demand and drug supply. 2022; [cited: 2023 Aug 11]. Available from: https://www.unodc.org/res/wdr2022/MS/WDR22_Booklet_2.pdf

Roberts A, Rogers J, Mason R, Siriwardena AN, Hogue T, Whitley GA, et al. Alcohol and other substance use during the COVID-19 pandemic: A systematic review. DAD 2021;229(Pt A): 109150. doi: 10.1016/j.drugalcdep.2021.109150.

Wiencek J, Colby J, Nichols J. Rapid assessment of drugs of abuse. Adv Clin Chem 2017;80:193-225. doi: 10.1016/bs.acc.2016.11.003.

Fu S. Adulterants in urine drug testing. Adv Clin Chem 2016;76:123-63. doi: 10.1016/bs.acc.2016.05.003.

Basiri MR, Behshid M, Najafi A, Alilou S, Mohebbi-Kamali H, Hosseindoust F, et al. Evaluation of abuse drugs and clinical laboratory tests variations in whole blood & urine samples of abusers. J Pharm Pharmacol 2018;6:69-76. doi: 10.17265/2328-2150/2018.01.008.

Atanasov V. Screening methods. Quantitative analysis In: Atanasov V, Ed.. Forensic toxicology - principles and practice. Sofia: Military Medical Academy; 2020. p. 51-69.

McCarberg BH, Kirsh KL, Passik SD. Clinicians' perspective on the use of immunoassay versus definitive laboratory quantitation methodologies for medication monitoring. J Pain Palliat Care Pharmacother 2014;28(3):255-8. doi: 10.3109/15360288.2014.938887.

Graziano S, Anzillotti L, Mannocchi G, Pichini S, Busardò FP. Screening methods for rapid determination of new psychoactive substances (NPS) in conventional and non-conventional biological matrices. J Pharm Biomed Anal. 2019;163:170-9. doi: 10.1016/j.jpba.2018.10.011.

Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83(1):66-76. doi: 10.4065/83.1.66.

Grafinger KE, Liechti ME, Liakoni E. Clinical value of analytical testing in patients presenting with new psychoactive substances intoxication. Br J Clin Pharmacol. 2020;86(3):429-36. doi: 10.1111/bcp.14115.

Reisfield GM, Goldberger BA, Bertholf RL. 'False-positive' and 'false-negative' test results in clinical urine drug testing. Bioanalysis. 2009;1(5):937-52. doi: 10.4155/bio.09.81.

Cherwinski K, Petti TA, Jekelis A. False methadone-positive urine drug screens in patients treated with quetiapine. JAACAP. 2007;46(4):435-6. doi: 10.1097/CHI.0b013e31802f5f1b.

Callaghan K, Rappaport DI. False-positive urine drug screen for benzodiazepines in a child taking fluoxetine. Pediatr Emerg Care. 2021;37(5):e283. doi: 10.1097/PEC.0000000000002434.

Anderson LA, Can a Drug Test Lead to a False Positive? 2021; [cited: 2023 Aug 11]. Available from: https://www.drugs.com/article/false-positive-drug-tests.html

Schwarz DA, George MP, Bluth MH. Toxicology in Addiction Medicine. Clin Lab Med 2016;36(4):685-92. doi: 10.1016/j.cll.2016.07.009.

Luethi D, Liechti ME. Designer drugs: mechanism of action and adverse effects. Arch Toxicol. 2020;94:1085–133. doi: 10.1007/s00204-020-02693-7.

Levine M, Lovecchio F. New designer drugs. Emerg. Med Clin North Am. 2021;39(3):677-687. doi: 10.1016/j.emc.2021.04.013.

Bates B. Drug screens fail accuracy tests 10% of time. Clin Psychiatry News. 2010; [cited: 2023 Aug 11]. Available from: https://cdn.mdedge.com/files/s3fs-public/issues/articles/70348_main_10.pdf

Weiss ST, Veach LJ, McGill W, Brent J. Rates and types of urine drug screen false negative results compared with confirmatory toxicology testing in major trauma patients. Clin Toxicol (Phila). 2022;60(10):1122-9. doi: 10.1080/15563650.2022.2117052.

Smith MP, Bluth MH. Common Interferences in Drug Testing. Clin Lab Med. 2016;36(4):663-71. doi: 10.1016/j.cll.2016.07.006.

Luzzi VI, Saunders AN, Koenig JW, Turk J, Lo SF, Garg UC, et al. Analytic performance of immunoassays for drugs of abuse below established cutoff values. Clin Chem 2004; 50(4): 717-722. https://doi.org/10.1373/clinchem.2003.028878

Schwebach A, Ball J. Urine drug screening: minimizing false-positives and false-negatives to optimize patient care. US Pharm. 2016;41(8):26-30.

Gerberich A. What drugs are likely to interfere with urine drug screens? 2021; [cited: 2023 Aug 11]. Available from: https://dig.pharmacy.uic.edu/faqs/2021-2/may-2021-faqs/what-drugs-are-likely-to-interfere-with-urine-drug-screens/

Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. J Anal Toxicol. 2014;38(7):387-96. doi: 10.1093/jat/bku075.

Cone EJ, Lange R, Darwin WD. In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results. J Anal Toxicol. 1998; 22(6):460-73. doi: 10.1093/jat/22.6.460.

Jaffee WB, Trucco E, Levy S, Weiss RD. Is this urine really negative? A systematic review of tampering methods in urine drug screening and testing. J Subst Abuse Treat. 2007;33(1):33-42. doi: 10.1016/j.jsat.2006.11.008.

Dasgupta A. Synthetic urine, flushing, detoxifying, and related agents for beating urine drug tests: are they effective? In: Dasgupta A, editor. Beating drug tests and defending positive results. Totowa: Humana Press; 2010. p. 45–60. doi: 10.1007/978-1-60761-527-9_4.

Dasgupta A. The effects of adulterants and selected ingested compounds on drugs-of-abuse testing in urine. Am J Clin Pathol. 2007;128(3):491-503. doi: 10.1309/FQY06F8XKTQPM149.

De Fazio S, Gallelli L, De Siena A, De Sarro G, Scordo MG. Role of CYP3A5 in abnormal clearance of methadone. Ann Pharmacother. 2008;42(6):893-7. doi: 10.1345/aph.1K539.

Lee HK, Lewis LD, Tsongalis GJ, McMullin M, Schur BC, Wong SH, et al. Negative urine opioid screening caused by rifampin-mediated induction of oxycodone hepatic metabolism. Clin Chim Acta. 2006;367(1-2):196-200. doi: 10.1016/j.cca.2005.11.030.

Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA. Commonly prescribed medications and potential false-positive urine drug screens. Am J Health Syst Pharm. 2010;67(16):1344-50. doi: 10.2146/ajhp090477.

Semeniuk U, Potocka-Banaś B, Jasionowicz E, Borowiak K, Janus T. CEDIA method in amphetamine and cannabinoid analysis – potential applications in forensic toxicology blood tests. Pomeranian J Life Sci. 2020;66(2):61-4. doi: 10.21164/pomjlifesci.699.

Cox KL, Devanarayan V, Kriauciunas A, Manetta J, Montrose C, Sittampalam S. Immunoassay Methods. 2012; [cited: 2023 Aug 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92434/

Moyer TP, Palmen MA, Johnson P, Charlson JR, Ellefson PJ. Marijuana testing--how good is it? Mayo Clin Proc. 1987;62(5):413-7. doi: 10.1016/s0025-6196(12)65447-0.

Mikkelsen SL, Ash KO. Adulterants causing false negatives in illicit drug testing. Clin Chem. 1988;34(11):2333-6. doi: 10.1093/clinchem/34.11.2333.

Weatherspoon D. Trying to ‘Clean’ Your System Before a Drug Test? Skip the Vinegar. 2021; [cited: 2023 Aug 11]. Available from: https://www.healthline.com/health/substance-use/does-vinegar-clean-your-system-in-24-hours

Mizrak S. Fraudulent methods causing false negatives in urine drug testing. Biomed J Sci Tech Res. 2019; 14(1): 10335-7. doi: 10.26717/BJSTR.2019.14.002481.

Schwarzhoff R, Cody JT. The effects of adulterating agents on FPIA analysis of urine for drugs of abuse. J Anal Toxicol. 1993;17(1):14-7. doi: 10.1093/jat/17.1.14.

Wu A. Urine adulteration and substitution prior to drugs of abuse testing. J Clin Ligand Assay. 2003; 26(1):11-8.

Paul BD, Jacobs A. Effects of oxidizing adulterants on detection of 11-nor-delta9-THC-9-carboxylic acid in urine. J Anal Toxicol. 2002;26(7):460-3. doi: 10.1093/jat/26.7.460.

Pham AQN, Kelly T, Fu S. Urine adulteration: can bleach be used to mask MDMA use? Anal Methods. 2013;5:3948–55. doi: 10.1039/C3AY40543E.

Pearson SD, Ash KO, Urry FM. Mechanism of false-negative urine cannabinoid immunoassay screens by Visine eyedrops. Clin Chem. 1989;35(4):636-8.

Tsai LS, ElSohly MA, Tsai SF, Murphy TP, Twarowska B, Salamone SJ. Investigation of nitrite adulteration on the immunoassay and GC-MS analysis of cannabinoids in urine specimens. J Anal Toxicol. 2000;24(8):708-14. doi: 10.1093/jat/24.8.708.

ElSohly MA, Feng S, Kopycki WJ, Murphy TP, Jones AB, Davis A, et al. A procedure to overcome interferences caused by the adulterant "Klear" in the GC-MS analysis of 11-nor-delta9-THC-9-COOH. J Anal Toxicol. 1997;21(3):240-2. doi: 10.1093/jat/21.3.240.

Valtier S, Cody JT. A procedure for the detection of Stealth adulterant in urine samples. Clin Lab Sci. 2002;15(2):111-5.

Goldberger BA, Caplan YH. Effect of glutaraldehyde (UrinAid) on detection of abused drugs in urine by immunoassay. Clin Chem. 1994;40(8):1605-6.

Gmeiner G, Geisendorfer T. Urine manipulation with liquid soap: A case report. Drug Test Anal. 2020;12(5):575-8. doi: 10.1002/dta.2780.

Kluge J, Rentzsch L, Remane D, Peters FT, Wissenbach DK. Systematic investigations of novel validity parameters in urine drug testing and prevalence of urine adulteration in a two-year cohort. Drug Test Anal. 2018;10(10):1536-42. doi: 10.1002/dta.2447.

Wissenbach DK, Steuer AE. Advances in testing for sample manipulation in clinical and forensic toxicology - Part A: urine samples. Anal Bioanal Chem. 2023;415:5101–5. doi: 10.1007/s00216-023-04711-w.

Nazaria K. Best Synthetic Urine Kits: Top 5 Fake Pee Brands To Pass a Drug Test. 2023; [cited: 2023 Aug 11]. Available from: https://www.newsdirect.com/guest-content/best-synthetic-urine

Embers DM, Ravishankar DA, Din A, Sethi R. Synthetic Urines in a Buprenorphine Clinic. Kans J Med. 2019;12(4):146-7.

USNRC. 26.111 Checking the acceptability of the urine specimen. 2022; [cited: 2023 Aug 11]. Available from: https://www.nrc.gov/reading-rm/doc-collections/cfr/part026/part026-0111.html

Casavant MJ. Urine drug screening in adolescents. Pediatr Clin North Am. 2002;49(2):317-27. doi: 10.1016/s0031-3955(01)00006-2.

Wyness SP, Hunsaker JJH, Snow TM, Genzen JR. Evaluation and analytical validation of a handheld digital refractometer for urine specific gravity measurement. Pract Lab Med. 2016; 5:65-74. doi: 10.1016/j.plabm.2016.06.001.

Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage. 2004;27(3):260-7. doi: 10.1016/j.jpainsymman.2003.07.008.

Musile G, Agard Y, Pesavento S, De Palo EF, Dorizzi RM, Bortolotti F. An origami microfluidic paper device for on-site assessment of urine tampering. First use of Nessler's reagent for the colorimetric determination of creatinine. Anal Chim Acta. 2023;1237:340610. doi: 10.1016/j.aca.2022.340610.

Franz S, Skopp G, Musshoff F. The effect of creatine ingestion on urinary creatinine concentration: Does supplementation mask a heavy dilution? Drug Test Anal. 2022;14(1):162-8. doi: 10.1002/dta.3165.

Committee for Medicinal Products for Human Use (EMA). Assessment report; Referral under Article 31 of Directive 2001/83/EC, metamizole-containing medicinal products. 2019; [cited: 2023 Aug 11]. Available from: https://www.ema.europa.eu/en/documents/referral/metamizole-article-31-referral-chmp-assessment-report_en.pdf

Rifampin (Oral Route). Mayo Clinic. 2023; [cited: 2023 Aug 11]. Available from: https://www.mayoclinic.org/drugs-supplements/rifampin-oral-route/precautions/drg-20065839

The Meaning Behind the Color of Urine. Urology Care Foundation. 2018; [cited: 2023 Aug 11]. Available from: https://www.urologyhealth.org/healthy-living/care-blog/2018/the-meaning-behind-the-color-of-urine

Riahi-Zanjani B. False positive and false negative results in urine drug screening tests: tampering methods and specimen integrity tests. PhOL. 2014;103:102-8.

Aydoğdu M, Akgür SA. Urine drug-testing tampering approaches: Turkish probationers. Med Sci Law. 2021;61(1):6-13. doi: 10.1177/0025802420956453.

Dasgupta A. Adulteration of Drugs-of-Abuse Specimens. In: Wong RC, Tse HY, editors. Drugs of Abuse. Forensic Science and Medicine. Totowa: Humana Press; 2005. p. 217–32. doi: 10.1007/978-1-59259-951-6_13.

Dasgupta A. How People Try to Beat Drug Testing. Issues with Urinary Adulterants and their Detection. Clinical Laboratory News. 2015; [cited: 2023 Aug 11]. Available from: https://www.aacc.org/cln/articles/2015/february/drug-testing

Wu AH, Bristol B, Sexton K, Cassella-McLane G, Holtman V, Hill DW. Adulteration of urine by "Urine Luck". Clin Chem. 1999;45(7):1051-7.

Thevis M, Geyer H, Sigmund G, Schänzer W. Sports drug testing: Analytical aspects of selected cases of suspected, purported, and proven urine manipulation. J Pharm Biomed Anal. 2012;57:26-32. doi: 10.1016/j.jpba.2011.09.002.

Deventer K, Delbeke FT, Roels K, Van Eenoo P. Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography-tandem mass spectrometry. Biomed Chromatogr. 2002;16(8):529-35. doi: 10.1002/bmc.201.




DOI: http://dx.doi.org/10.14748/ssp.v10i1.9227

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About The Author

Stanila Stoeva
Medical university of Varna
Bulgaria

Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy

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