Common Causes of False Positive and False Negative Results in Amphetamine Screening Tests

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Abstract

The need for toxicological screening of amphetamine users is growing in parallel with its increasing abuse. At the same time, it turns out that these substances most often give false results in rapid drug immunoassay. Therefore, the aim of the present work was to investigate the sources of false positive or false negative results. For this purpose, an analysis of the literature sources in the databases of Google Scholar, PubMed, and Science Direct, was made. The results showed that a number of prescription or OTC medications can cause false positive results due to cross-reactivity (ephedrine, pseudoephedrine, labetalol, metoprolol, some antidepressants, metformin, ranitidine, ofloxacin, selegiline, etc.). In this regard, alternative medications for patients who often have to undergo such screening have been proposed. Some possibilities of unintentionally or intentionally inducing false negative results have also been highlighted. Popular approaches to fooling the screening test are diluting the urine, adding adulterants (marketed products or homemade chemicals), and providing foreign or synthetic urine. Summarizing the possible sources of errors in drug screening is expected to objectify the interpretation of the obtained results.

Graphical Abstract

[1]
UNODC. Booklet 4 - Drug market trends of Cocaine, Amphetamine- type stimulants and New Psychoactive Substances World Drug Report., 2022. Available from: https://www.unodc.org/unodc/en/data-and-analysis/wdr-2022_booklet-4.html (Accessed on: July 30, 2023)
[2]
Roberts, A.; Rogers, J.; Mason, R.; Siriwardena, A.N.; Hogue, T.; Whitley, G.A.; Law, G.R. . Alcohol and other substance use during the COVID-19 pandemic: A systematic review. Drug Alcohol Depend., 2021, 229((Pt A)), 109150.
[http://dx.doi.org/10.1016/j.drugalcdep.2021.109150] [PMID: 34749198]
[3]
Kassim, F.M. Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits. Hum. Psychopharmacol., 2023, 38(1), e2856.
[http://dx.doi.org/10.1002/hup.2856] [PMID: 36251504]
[4]
Nickell, J.R.; Siripurapu, K.B.; Vartak, A.; Crooks, P.A.; Dwoskin, L.P. The vesicular monoamine transporter-2: an important pharmacological target for the discovery of novel therapeutics to treat methamphetamine abuse. Adv. Pharmacol., 2014, 69, 71-106.
[http://dx.doi.org/10.1016/B978-0-12-420118-7.00002-0] [PMID: 24484975]
[5]
Berman, S.; O’Neill, J.; Fears, S.; Bartzokis, G.; London, E.D. Abuse of amphetamines and structural abnormalities in the brain. Ann. N. Y. Acad. Sci., 2008, 1141(1), 195-220.
[http://dx.doi.org/10.1196/annals.1441.031] [PMID: 18991959]
[6]
Kraemer, T.; Maurer, H.H. Toxicokinetics of amphetamines: Metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Ther. Drug Monit., 2002, 24(2), 277-289.
[http://dx.doi.org/10.1097/00007691-200204000-00009] [PMID: 11897973]
[7]
Sanap, S.N.; Bisen, A.C.; Kedar, A.; Agrawal, S.; Bhatta, R.S. Recent update on pharmacokinetics and drug metabolism in CNS-based drug discovery. Curr. Pharm. Des., 2023, 29(20), 1602-1616.
[http://dx.doi.org/10.2174/1381612829666230707121415] [PMID: 37424342]
[8]
Capela, J.P.; Costa, V.M. Pharmacology and toxicology of amphetamine-type stimulants. Future Pharmacol., 2023, 3(2), 515-516.
[http://dx.doi.org/10.3390/futurepharmacol3020032]
[9]
Spyres, M.B.; Jang, D.H. Amphetamines. In: Goldfrank’s Toxicologic Emergencies, 11th ed; Nelson, L.; Hoffman, R.; Howland, M.; Lewin, N.; Smith, S.W.; Goldfrank, L., Eds.; McGrow Hill: New York; , 2019, pp. 1099-1110.
[10]
Brahm, N.C.; Yeager, L.L.; Fox, M.D.; Farmer, K.C.; Palmer, T.A. Commonly prescribed medications and potential false-positive urine drug screens. Am. J. Health Syst. Pharm., 2010, 67(16), 1344-1350.
[http://dx.doi.org/10.2146/ajhp090477] [PMID: 20689123]
[11]
Wiencek, J.R.; Colby, J.M.; Nichols, J.H. Rapid assessment of drugs of abuse. Adv. Clin. Chem., 2017, 80, 193-225.
[http://dx.doi.org/10.1016/bs.acc.2016.11.003] [PMID: 28431640]
[12]
Maurer, H.H. Analytical toxicolog. In: Molecular, Clinical and Environmental Toxicology. Experientia Supplementum; Luch, A., Ed.; Birkhäuser: Basel, 2010, pp. 317-338.
[http://dx.doi.org/10.1007/978-3-7643-8338-1_9]
[13]
Atanasov, V. Screening methods. Quantitative analysis. In: Forensic toxicology - principles and practice; Atanasov, V., Ed.; Military Medical Academy: Sofia, 2020, pp. 51-69.
[14]
McDermott, S.D. Drugs of Abuse. In: Clarke’s Analysis of Drugs and Poisons, 4th ed; Moffat, A.; Osselton, D.; Widdop, B., Eds.; Pharmaceutical Press: London, 2011; pp. 190-207.
[15]
Topic, I.C.H. Validation of analytical prrocedures: Definitions and methodology: Ich harmonised tripartite guideline., 1995. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-2-r1-validation-analytical-procedures-text-methodology-step-5_en.pdf (Accessed on: Aug 30, 2023).
[16]
EMA Guideline on bioanalytical method validation, 2011. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf (Accessed on: Aug 30, 2023).
[17]
Yüksel, B.; Şen, N. Development and validation of a GC-FID method for determination of cocaine in illicit drug samples. Marmara Pharm. J., 2018, 22, 511-518.
[18]
Yüksel, B.; Öncü, T.; Şen, N. Assessing caffeine levels in soft beverages available in Istanbul, Turkey: An LC-MS/MS application in food toxicology. Toxicol. Anal. et Clin., 2023, 35(1), 33-43.
[http://dx.doi.org/10.1016/j.toxac.2022.08.004]
[19]
Öncü, T.; Yüksel, B.; Binay, E.; Şen, N. Investigation of nitrosamine impurities in certain Sartan group medicinal products available in Istanbul Türkiye. Ann. Pharm. Fr., 2023, 2013.
[20]
Uges, D.R.A. Hospital toxicology.In: Clarke’s Analysis of Drugs and Poisons, 4th ed; Moffat, A.; Osselton, D.; Widdop, B., Eds.; Pharmaceutical Press: London; , 2011, pp. 3-58.
[21]
Jiang, X.; Lillehoj, P.B. Lateral flow immunochromatographic assay on a single piece of paper. Analyst, 2021, 146(3), 1084-1090.
[http://dx.doi.org/10.1039/D0AN02073G] [PMID: 33347520]
[22]
Park, J. Lateral flow immunoassay reader technologies for quantitative point-of-care testing. Sensors, 2022, 22(19), 7398.
[http://dx.doi.org/10.3390/s22197398] [PMID: 36236497]
[23]
Koczula, K.M.; Gallotta, A. Lateral flow assays. In: Essays in Biochemistry; Koczula, K.M.; Gallotta, A., Eds.; Portland Press: London., 2016, 60, 111-120.
[24]
Qriouet, Z.; Cherrah, Y.; Sefrioui, H.; Qmichou, Z. Monoclonal antibodies application in lateral flow immunochromatographic assays for drugs of abuse detection. Molecules, 2021, 26(4), 1058.
[http://dx.doi.org/10.3390/molecules26041058] [PMID: 33670468]
[25]
Callaghan, K.; Rappaport, D.I. False-positive urine drug screen for benzodiazepines in a child taking fluoxetine. Pediatr. Emerg. Care, 2021, 37(5), e283.
[http://dx.doi.org/10.1097/PEC.0000000000002434] [PMID: 33903296]
[26]
Cherwinski, K.; Petti, T.A.; Jekelis, A. False methadone-positive urine drug screens in patients treated with quetiapine. J. Am. Acad. Child Adolesc. Psychiatry, 2007, 46(4), 435-436.
[http://dx.doi.org/10.1097/CHI.0b013e31802f5f1b] [PMID: 17420676]
[27]
Reisfield, G.M.; Goldberger, B.A.; Bertholf, R.L. ‘False-positive’ and ‘false-negative’ test results in clinical urine drug testing. Bioanalysis, 2009, 1(5), 937-952.
[http://dx.doi.org/10.4155/bio.09.81] [PMID: 21083064]
[28]
Moeller, K.E.; Lee, K.C.; Kissack, J.C. Urine drug screening: Practical guide for clinicians. Mayo Clin. Proc., 2008, 83(1), 66-76.
[http://dx.doi.org/10.4065/83.1.66] [PMID: 18174009]
[29]
Casey, E.R.; Scott, M.G.; Tang, S.; Mullins, M.E. Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay. J. Med. Toxicol., 2011, 7(2), 105-108.
[http://dx.doi.org/10.1007/s13181-010-0131-5] [PMID: 21191682]
[30]
Saitman, A.; Park, H.D.; Fitzgerald, R.L. False-positive interferences of common urine drug screen immunoassays: A review. J. Anal. Toxicol., 2014, 38(7), 387-396.
[http://dx.doi.org/10.1093/jat/bku075] [PMID: 24986836]
[31]
Yee, L.M.; Wu, D. False-positive amphetamine toxicology screen results in three pregnant women using labetalol. Obstet. Gynecol., 2011, 117(2), 503-506.
[http://dx.doi.org/10.1097/AOG.0b013e318206c07c] [PMID: 21252805]
[32]
Hughey, J.J.; Colby, J.M. Discovering cross-reactivity in urine drug screening immunoassays through large-scale analysis of electronic health records. Clin. Chem., 2019, 65(12), 1522-1531.
[http://dx.doi.org/10.1373/clinchem.2019.305409] [PMID: 31578215]
[33]
Leclercq, M.; Soichot, M.; Delhotal-Landes, B.; Bourgogne, E.; Gourlain, H.; Mégarbane, B.; Labat, L. False positive amphetamines and 3,4-methylenedioxymethamphetamine immunoassays in the presence of metoprolol—two cases reported in clinical toxicology. J. Anal. Toxicol., 2020, 44(2), 200-205.
[http://dx.doi.org/10.1093/jat/bkz051] [PMID: 31384953]
[34]
Rivas-Coppola, M.S.; Patterson, A.L.; Morgan, R.; Wheless, J.W. Bupropion overdose presenting as status epilepticus in an infant. Pediatr. Neurol., 2015, 53(3), 257-261.
[http://dx.doi.org/10.1016/j.pediatrneurol.2015.05.018] [PMID: 26183178]
[35]
Baron, J.M.; Griggs, D.A.; Nixon, A.L.; Long, W.H.; Flood, J.G. The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results. J. Anal. Toxicol., 2011, 35(6), 364-368.
[http://dx.doi.org/10.1093/anatox/35.6.364] [PMID: 21740694]
[36]
Roberge, R.J.; Luellen, J.R.; Reed, S. False-positive amphetamine screen following a trazodone overdose. J. Toxicol. Clin. Toxicol., 2001, 39(2), 181-182.
[http://dx.doi.org/10.1081/CLT-100103839] [PMID: 11407508]
[37]
Schwebach, A.; Ball, J. Urine drug screening: Minimizing false-positives and false-negatives to optimize patient care. US Pharm., 2016, 41, 6-30.
[38]
Romberg, R.W.; Needleman, S.B.; Jacob Snyder, J.; Greedan, A. Methamphetamine and amphetamine derived from the metabolism of selegiline. J. Forensic Sci., 1995, 40(6), 13885J.
[http://dx.doi.org/10.1520/JFS13885J] [PMID: 8522918]
[39]
Liu, L.; Wheeler, S.E.; Rymer, J.A.; Lower, D.; Zona, J.; Peck Palmer, O.M.; Tamama, K.; Tamama, K. Ranitidine interference with standard amphetamine immunoassay. Clin. Chim. Acta, 2015, 438, 307-308.
[http://dx.doi.org/10.1016/j.cca.2014.09.012] [PMID: 25242739]
[40]
Fucci, N. False positive results for amphetamine in urine of a patient with diabetes mellitus. Forensic Sci. Int., 2012, 223(1-3), e60.
[http://dx.doi.org/10.1016/j.forsciint.2012.08.010] [PMID: 23026178]
[41]
Nomier, M.; Al-Huseini, H. False-positive TDxFLx urine amphetamine/metamphetamine II assay from Ofloxacin. SPJ, 2004, 12, 42-46.
[42]
Jaffee, W.B.; Trucco, E.; Levy, S.; Weiss, R.D. 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.
[http://dx.doi.org/10.1016/j.jsat.2006.11.008] [PMID: 17588487]
[43]
Wu, A.H.B.; Bristol, B.; Sexton, K.; Cassella-McLane, G.; Holtman, V.; Hill, D.W. Adulteration of urine by “urine luck”. Clin. Chem., 1999, 45(7), 1051-1057.
[http://dx.doi.org/10.1093/clinchem/45.7.1051] [PMID: 10388482]
[44]
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.
[http://dx.doi.org/10.1309/FQY06F8XKTQPM149] [PMID: 17709324]
[45]
Schwarzhoff, R.; Cody, J.T. The effects of adulterating agents on FPIA analysis of urine for drugs of abuse. J. Anal. Toxicol., 1993, 17(1), 14-17.
[http://dx.doi.org/10.1093/jat/17.1.14] [PMID: 8429620]
[46]
Mikkelsen, S.L.; Ash, K.O. Adulterants causing false negatives in illicit drug testing. Clin. Chem., 1988, 34(11), 2333-2336.
[http://dx.doi.org/10.1093/clinchem/34.11.2333] [PMID: 3052928]
[47]
Lin, C.N.; Strathmann, F.G. Elevated urine zinc concentration reduces the detection of methamphetamine, cocaine, THC and opiates in urine by EMIT. J. Anal. Toxicol., 2013, 37(9), 665-669.
[http://dx.doi.org/10.1093/jat/bkt056] [PMID: 23843421]
[48]
Wong, R. The effect of adulterants on urine screen for drugs of abuse: Detection by an on-site dipstick device. Am. Clin. Lab., 2002, 21(1), 37-39.
[PMID: 11975450]
[49]
Tsai, S.C.J.; ElSohly, M.A.; Dubrovsky, T.; Twarowska, B.; Towt, J.; Salamone, S.J. Determination of five abused drugs in nitrite-adulterated urine by immunoassays and gas chromatography-mass spectrometry. J. Anal. Toxicol., 1998, 22(6), 474-480.
[http://dx.doi.org/10.1093/jat/22.6.474] [PMID: 9788522]
[50]
Fu, S. Adulterants in urine drug testing. Adv. Clin. Chem., 2016, 76, 123-163.
[http://dx.doi.org/10.1016/bs.acc.2016.05.003] [PMID: 27645818]
[51]
Aydoğdu, M.; Akgür, S.A. Urine drug-testing tampering approaches: Turkish probationers. Med. Sci. Law, 2021, 61(1), 6-13.
[http://dx.doi.org/10.1177/0025802420956453] [PMID: 32924786]
[52]
Chou, S.L.; Giang, Y.S. Influences of seven Taiwan-produced adulterants on the fluorescence polarization immunoassay (FPIA) of amphetamines in urine. Forensic Sci. J., 2008, 7, 1-12.
[53]
Rajšić, I.; Javorac, D.; Tatović, S.; Repić, A.; Đukić-Ćosić, D.; Đorđević, S.; Lukić, V.; Bulat, Z. Effect of urine adulterants on commercial drug abuse screening test strip results. Archives Industr. Hygi. Toxicol., 2020, 71(1), 87-93.
[http://dx.doi.org/10.2478/aiht-2020-71-3315] [PMID: 32597134]
[54]
Pham, A.Q.N.; Kelly, T.; Fu, S. Urine adulteration: Can bleach be used to mask MDMA use? Anal. Methods, 2013, 5(16), 3948-3955.
[http://dx.doi.org/10.1039/C3AY40543E]
[55]
Smith, M.P.; Bluth, M.H. Common interferences in drug testing. Clin. Lab. Med., 2016, 36(4), 663-671.
[http://dx.doi.org/10.1016/j.cll.2016.07.006] [PMID: 27842784]