Urine drug screening: practical guide for clinicians.

Drug testing, commonly used in health care, workplace, and criminal settings, has become widespread during the past decade. Urine drug screens have been the most common method for analysis because of ease of sampling. The simplicity of use and access to rapid results have increased demand for and use of immunoassays; however, these assays are not perfect. False-positive results of immunoassays can lead to serious medical or social consequences if results are not confirmed by secondary analysis, such as gas chromatography-mass spectrometry. The Department of Health and Human Services' guidelines for the workplace require testing for the following 5 substances: amphetamines, cannabinoids, cocaine, opiates, and phencyclidine. This article discusses potential false-positive results and false-negative results that occur with immunoassays of these substances and with alcohol, benzodiazepines, and tricyclic antidepressants. Other pitfalls, such as adulteration, substitution, and dilution of urine samples, are discussed. Pragmatic concepts summarized in this article should minimize the potential risks of misinterpreting urine drug screens.

[1]  A. Rothschild,et al.  Comparison of the frequency of behavioral disinhibition on alprazolam, clonazepam, or no benzodiazepine in hospitalized psychiatric patients. , 2000, Journal of clinical psychopharmacology.

[2]  A. Warner,et al.  Interference of common household chemicals in immunoassay methods for drugs of abuse. , 1989, Clinical chemistry.

[3]  Rania M. Seliem,et al.  A positive drug test in the pain management patient: deception or herbal cross-reactivity? , 2002, Clinical chemistry.

[4]  R. Meatherall,et al.  False-positive EMIT II opiates from ofloxacin. , 1997, Therapeutic drug monitoring.

[5]  A. Dasgupta,et al.  Comparison of spot tests with AdultaCheck 6 and Intect 7 urine test strips for detecting the presence of adulterants in urine specimens. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[6]  A. Verstraete,et al.  Detection Times of Drugs of Abuse in Blood, Urine, and Oral Fluid , 2004, Therapeutic drug monitoring.

[7]  D. Burger,et al.  False-positive results in urine drug screening in healthy volunteers participating in phase 1 studies with efavirenz and rifampin. , 2006, Therapeutic drug monitoring.

[8]  J. Haidar,et al.  Rifampin interference with opiate immunoassays. , 2002, Clinical chemistry.

[9]  J. Osterloh Testing for Drugs of Abuse , 1993, Clinical pharmacokinetics.

[10]  E. Cone,et al.  Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays. , 1993, Journal of analytical toxicology.

[11]  C. Wolf,et al.  Falsely elevated imipramine levels in a patient taking quetiapine. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  E. Uhlenhuth,et al.  International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: IV. Therapeutic dose dependence and abuse liability of benzodiazepines in the long-term treatment of anxiety disorders. , 1999, Journal of clinical psychopharmacology.

[13]  K. Olsen,et al.  Metabolites of chlorpromazine and brompheniramine may cause false-positive urine amphetamine results with monoclonal EMIT d.a.u. immunoassay. , 1992, Clinical chemistry.

[14]  T. Mencken,et al.  False-positive immunochemical screen for methadone attributable to metabolites of verapamil. , 1998, Clinical chemistry.

[15]  Green Kb,et al.  Medical Review Officer Interpretation of Urine Drug Test Results. , 1995 .

[16]  G. Sloop,et al.  False-positive postmortem EMIT drugs-of-abuse assay due to lactate dehydrogenase and lactate in urine. , 1995, Journal of analytical toxicology.

[17]  S. Manzi,et al.  Methylphenidate produces a false-positive urine amphetamine screen. , 2002, Pediatric emergency care.

[18]  R. Schwartz,et al.  MDMA (ecstasy) and the rave: a review. , 1997, Pediatrics.

[19]  A. P. Mason,et al.  Passive inhalation of marihuana smoke and urinary excretion of cannabinoids , 1983, Clinical pharmacology and therapeutics.

[20]  A. Nice,et al.  False-positive urine amphetamine screen with ritodrine. , 1989, Clinical chemistry.

[21]  Susan Budavari,et al.  The Merck index : an encyclopedia of chemicals, drugs, and biologicals , 1983 .

[22]  P. Sugarman Psychotropic Drug Handbook , 1988 .

[23]  G. M. Simpson,et al.  Critical interpretation of urinary phencyclidine monitoring. , 1984, Advances in alcohol & substance abuse.

[24]  S. B. Needleman,et al.  Methamphetamine and amphetamine derived from the metabolism of selegiline. , 1995, Journal of forensic sciences.

[25]  D. Lin,et al.  Performance characteristics of selected immunoassays for preliminary test of 3,4-methylenedioxymethamphetamine, methamphetamine, and related drugs in urine specimens. , 2003, Journal of analytical toxicology.

[26]  M. Pulini False-positive benzodiazepine urine test due to oxaprozin. , 1995, JAMA.

[27]  B. Ludes,et al.  Windows of Detection of Tetrazepam in Urine, Oral Fluid, Beard, and Hair, With a Special Focus on Drug-Facilitated Crimes , 2005, Therapeutic drug monitoring.

[28]  B. Ludes,et al.  Testing for the Undetectable in Drug-Facilitated Sexual Assault Using Hair Analyzed by Tandem Mass Spectrometry as Evidence , 2004, Therapeutic drug monitoring.

[29]  D. Dietzen,et al.  Analytic performance of immunoassays for drugs of abuse below established cutoff values. , 2004, Clinical chemistry.

[30]  William E. Cohen,et al.  Uppers, Downers, All Arounders: Physical and Mental Effects of Psychoactive Drugs , 1996 .

[31]  L. Brace,et al.  Coca tea consumption causes positive urine cocaine assay , 2006, European journal of emergency medicine : official journal of the European Society for Emergency Medicine.

[32]  D. Colbert Possible explanation for trimethobenzamide cross-reaction in immunoassays of amphetamine/methamphetamine. , 1994, Clinical chemistry.

[33]  G. Koren,et al.  Carbamazepine interference with an immune assay for tricyclic antidepressants in plasma. , 1998, Journal of toxicology. Clinical toxicology.

[34]  S D Ferrara,et al.  Drugs-of-abuse testing in urine: statistical approach and experimental comparison of immunochemical and chromatographic techniques. , 1994, Journal of analytical toxicology.

[35]  I. Grant,et al.  Characterization of interference with 6 commercial delta9-tetrahydrocannabinol immunoassays by efavirenz (glucuronide) in urine. , 2006, Clinical chemistry.

[36]  M. Smith,et al.  A practical approach to determine cutoff concentrations for opiate testing with simultaneous detection of codeine, morphine, and 6-acetylmorphine in urine. , 1999, Clinical chemistry.

[37]  G. Leson,et al.  Evaluating the impact of hemp food consumption on workplace drug tests. , 2001, Journal of analytical toxicology.

[38]  A. Zebelman,et al.  Clinical inquiries. What common substances can cause false positives on urine screens for drugs of abuse? , 2006, The Journal of family practice.

[39]  G. Grinstead Ranitidine and high concentrations of phenylpropanolamine cross react in the EMIT monoclonal amphetamine/methamphetamine assay. , 1989, Clinical chemistry.

[40]  E. Cone,et al.  Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for drugs of abuse. , 1995, Journal of analytical toxicology.

[41]  D A Armbruster,et al.  Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. , 1993, Clinical chemistry.

[42]  M. Linder,et al.  Amphetamine positive toxicology screen secondary to bupropion , 2000, Depression and anxiety.

[43]  R. E. Struempler Excretion of codeine and morphine following ingestion of poppy seeds. , 1987, Journal of analytical toxicology.

[44]  G. M. Ellis,et al.  Excretion patterns of cannabinoid metabolites after last use in a group of chronic users , 1985, Clinical pharmacology and therapeutics.

[45]  H. Meltzer,et al.  Psychopharmacology : the third generation of progress , 1987 .

[46]  John T Cody,et al.  Precursor Medications as a Source of Methamphetamine and/or Amphetamine Positive Drug Testing Results , 2002, Journal of occupational and environmental medicine.

[47]  Amadeo J Pesce,et al.  Urine drug screening in the medical setting. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[48]  A. Smogorzewska,et al.  Postmortem Urine Immunoassay Showing False-Positive Phencyclidine Reactivity in a Case of Fatal Tramadol Overdose , 2006, The American journal of forensic medicine and pathology.

[49]  V. Chiang,et al.  Carbamazepine overdose recognized by a tricyclic antidepressant assay. , 2001, Pediatrics.

[50]  D. Rollins,et al.  Investigation of interference by nonsteroidal anti-inflammatory drugs in urine tests for abused drugs. , 1990, Clinical chemistry.

[51]  J. Flood,et al.  Bupropion metabolites produce false-positive urine amphetamine results. , 1995, Clinical chemistry.

[52]  A. Alt,et al.  Improvement of ethyl glucuronide determination in human urine and serum samples by solid-phase extraction. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

[53]  A. Fraser,et al.  Oxaprozin cross-reactivity in three commercial immunoassays for benzodiazepines in urine. , 1998, Journal of analytical toxicology.

[54]  E. Ortiz Jiménez,et al.  Presence of rifampicin in urine causes cross-reactivity with opiates using the KIMS method. , 1995, Journal of analytical toxicology.

[55]  W. Rabl,et al.  Medicolegal aspects of tetrazepam metabolism , 2007, International Journal of Legal Medicine.

[56]  J. Schussler,et al.  Quetiapine and falsely elevated nortriptyline level. , 2003, The American journal of psychiatry.

[57]  K. Merigian,et al.  Doxepin causing false-positive urine test for amphetamine. , 1993, Annals of emergency medicine.

[58]  Tests for drugs of abuse. , 2002, The Medical letter on drugs and therapeutics.

[59]  G. Zomer,et al.  Determination of 6-acetylmorphine in urine as a specific marker for heroin abuse by high-performance liquid chromatography with fluorescence detection , 1985 .

[60]  A. Jones Urine as a Biological Specimen for Forensic Analysis of Alcohol and Variability in the Urine-to-Blood Relationship , 2006, Toxicological reviews.

[61]  J. Rainio,et al.  Cocaine found in a child’s hair due to environmental exposure? , 2004, International Journal of Legal Medicine.

[62]  Y. Caplan,et al.  Isometheptene cross reacts in the EMIT amphetamine assay. , 1987, Clinical chemistry.

[63]  M. Casavant Urine drug screening in adolescents. , 2002, Pediatric clinics of North America.

[64]  A. Saxon,et al.  Quetiapine and false-positive urine drug testing for tricyclic antidepressants. , 2000, The American journal of psychiatry.

[65]  P. Peng,et al.  A labetalol metabolite with analytical characteristics resembling amphetamines. , 1995, Journal of analytical toxicology.

[66]  A. Sorisky,et al.  Positive diphenhydramine interference in the EMIT-st assay for tricyclic antidepressants in serum. , 1986, Clinical chemistry.

[67]  R. Gupta,et al.  Determination of phencyclidine (PCP) in urine and illicit street drug samples. , 1975, Clinical toxicology.

[68]  A. Dasgupta,et al.  False-positive Serum Tricyclic Antidepressant Concentrations Using Fluorescence Polarization Immunoassay Due to the Presence of Hydroxyzine and Cetirizine , 2007, Therapeutic drug monitoring.

[69]  R. Roberge,et al.  False-Positive Amphetamine Screen Following a Trazodone Overdose , 2001, Journal of toxicology. Clinical toxicology.

[70]  F. Wians,et al.  False-positive serum tricyclic antidepressant screen with cyproheptadine. , 1993, Clinical chemistry.

[71]  A. Poklis,et al.  Response of EMIT Amphetamine Immunoassays to Urinary Desoxyephedrine Following Vicks Inhaler Use , 1995, Therapeutic drug monitoring.

[72]  K. Merigian,et al.  Desipramine and amantadine causing false-positive urine test for amphetamine. , 1993, Annals of emergency medicine.

[73]  A. Wu,et al.  False-positive phencyclidine immunoassay results caused by venlafaxine and O-desmethylvenlafaxine. , 2002, Clinical chemistry.

[74]  L. Shaw,et al.  Evaluation of Tricyclic Antidepressant False Positivity in a Pediatric Case of Cyproheptadine (Periactin) Overdose , 2003, Therapeutic drug monitoring.

[75]  N. V. Van Hoey Effect of cyclobenzaprine on tricyclic antidepressant assays. , 2005, The Annals of pharmacotherapy.

[76]  D. Colbert Drug abuse screening with immunoassays: unexpected cross-reactivities and other pitfalls. , 1994, British journal of biomedical science.

[77]  G. Eliopoulos,et al.  Quinolones and false-positive urine screening for opiates by immunoassay technology. , 2001, JAMA.

[78]  K. Klette,et al.  Evaluation of ephedrine, pseudoephedrine and phenylpropanolamine concentrations in human urine samples and a comparison of the specificity of DRI amphetamines and Abuscreen online (KIMS) amphetamines screening immunoassays. , 2004, Journal of forensic sciences.

[79]  N. Samyn,et al.  Detection of diazepam in urine, hair and preserved oral fluid samples with LC-MS-MS after single and repeated administration of Myolastan® and Valium® , 2007, Analytical and bioanalytical chemistry.

[80]  E. Lee-Lewandrowski,et al.  Reduced interference by phenothiazines in amphetamine drug of abuse immunoassays. , 2006, Archives of pathology & laboratory medicine.

[81]  R. Baselt,et al.  Urinary excretion of methadone in man , 1972, Clinical pharmacology and therapeutics.

[82]  John Joseph Fenton,et al.  Toxicology: A Case-Oriented Approach , 2001 .

[83]  Randall C. Baselt,et al.  Disposition of toxic drugs and chemicals in man , 1982 .

[84]  L. Hourani,et al.  Results from the 2008 National Survey on Drug Use and Health: National Findings , 2007 .

[85]  S. Binder,et al.  Ranitidine interference with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay. , 1991, Journal of analytical toxicology.

[86]  D. Dietzen,et al.  Positive predictive values of abused drug immunoassays on the Beckman Synchron in a veteran population. , 2001, Journal of analytical toxicology.

[87]  J. Allen,et al.  The role of laboratory tests in alcoholism treatment. , 2001, Journal of substance abuse treatment.

[88]  K. Wolff,et al.  Benzodiazepine Misuse by Drug Addicts , 1997, Annals of clinical biochemistry.

[89]  R. Weiss,et al.  Is this urine really negative? A systematic review of tampering methods in urine drug screening and testing. , 2007, Journal of substance abuse treatment.

[90]  P. Steele,et al.  Massive Venlafaxine Overdose Resulted in a False Positive Abbott AxSYM® Urine Immunoassay for Phencyclidine , 2003, Journal of toxicology. Clinical toxicology.

[91]  M. Peace,et al.  Performance evaluation of three on-site adulterant detection devices for urine specimens. , 2002, Journal of analytical toxicology.

[92]  J. D. Batjer,et al.  Detection of morphine and codeine following consumption of poppy seeds. , 1987, Journal of analytical toxicology.

[93]  Colbert Dl Drug abuse screening with immunoassays: unexpected cross-reactivities and other pitfalls. , 1994 .

[94]  N. Hoey Effect of Cyclobenzaprine on Tricyclic Antidepressant Assays , 2005 .

[95]  J. Manno,et al.  Application of the Syva EMIT and Abbott TDx amphetamine immunoassays to the detection of 3,4-methylene-dioxymethamphetamine (MDMA) and 3,4-methylene-dioxyethamphetamine (MDEA) in urine. , 1990, Journal of analytical toxicology.

[96]  K. Kelly Ranitidine cross-reactivity in the EMIT d.a.u. Monoclonal Amphetamine/Methamphetamine Assay. , 1990, Clinical chemistry.

[97]  E. Miravalles,et al.  Rifampicin Causes False-Positive Immunoassay Results for Urine Opiates , 1998, Clinical chemistry and laboratory medicine.

[98]  H. Heit,et al.  Urine drug testing in pain medicine. , 2004, Journal of pain and symptom management.

[99]  A. Leino,et al.  Comparison of eight commercial on-site screening devices for drugs-of-abuse testing. , 2001, Scandinavian journal of clinical and laboratory investigation.

[100]  S. Guthrie,et al.  Clinical Issues Associated with Urine Testing of Substances of Abuse , 1997, Pharmacotherapy.

[101]  M. Shannon,et al.  False-positive tricyclic antidepressant drug screen results leading to the diagnosis of carbamazepine intoxication. , 2000, Pediatrics.

[102]  H. Van As,et al.  Rifampicin cross-reacts with opiate immunoassay. , 1999, Journal of Analytical Toxicology.

[103]  S. D. Pearson,et al.  Mechanism of false-negative urine cannabinoid immunoassay screens by Visine eyedrops. , 1989, Clinical chemistry.