Reliability of urine drug screens: when should you consult the laboratory

False-positive urine drug screens: What clinicians should know and when
the laboratory should be consulted
Stacy E. F. Melanson, MD, PhD, FCAP
Barbarajean Magnani, MD, PhD, FCAP
College of American Pathologists Toxicology Resource Committee
Urine drug screens (UDS) are frequently ordered on patients who exhibit
symptoms of intoxication, experience trauma or offer a history of drug ingestion.1
Rapid and accurate results are critical to manage patients effectively; however,
inconsistencies between the laboratory results and the clinical picture may be
present.
Consider the following scenarios: (1) A 60-year-old male tests positive for urine
amphetamine, but adamantly denies amphetamine use and (2) an 80-year-old
woman from a nursing home tests positive for urine opiates, but her list of
medications does not include opioids. How should these scenarios be handled?
Clinicians should understand what urine drug screens are designed to detect,
which compounds can cross-react and when to refer to the laboratory for further
testing or clarification.
Immunoassays for UDS are automated and offer rapid turnaround times.1,2 The
common drugs or classes of drugs in the UDS include amphetamines,
barbiturates, benzodiazepines, cannabinoids, cocaine metabolite, methadone,
opiates, phencyclidine and tricyclic antidepressants. Several different
immunoassay techniques and platforms are available.3 Depending on the assay,
an antibody is designed to detect a specific class of compounds (i.e.
barbiturates), a parent drug (i.e. methadone) or a metabolite (i.e.
benzoylecgonine, a metabolite of cocaine).
Qualitative results are based on a specific calibrator concentration. Positive
results reflect a concentration above the calibrator cutoff, while negative results
reflect concentrations below the cutoff and do not exclude the presence of drug
or metabolite. The antibody specificity varies within the drug class and each
individual drug, within the class, requires a different urine concentration to trigger
a positive result. Certain antibodies may also cross-react with medications
outside the target drug class, thus leading to false-positive results.
The extent of cross-reactivity depends on the manufacturer’s platform and the
assay cutoff. The EMIT II and Triage meters are two common platforms.4,5 The
table contains a list of potential interferents in each assay. In the EMIT II
NewsPath® Editor: Megan J. DiFurio, MD, FCAP This newsletter is produced in cooperation with the College of American Pathologists’ Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright 2006 platform, medications—such as ranitidine and drug metabolites of compounds,
such as chlorpromazine and bupropion—can cross-react in the amphetamine
assay.6,7 Therapeutic concentrations of the fluoroquinolone antibiotics, ofloxacin
and levofloxacin, can interfere in the EMIT II opioid assay.4
Over-the-counter remedies can produce false-positive results in the EMIT II
phencyclidine and benzodiazepine assays and the Triage cannabinoid assay.4,5
The muscle relaxant cyclobenzaprine can cross-react in the Triage tricyclic
assay.5 Neither the EMIT II nor the Triage has reported false positives in the
barbiturate, methadone or cocaine assay.
Clinicians should appreciate the limitations of UDS in the medical setting, and
consider potential interferences. If a physician suspects a false positive, the
laboratory should be notified and the specimen should be sent for confirmatory
testing. In the scenarios above, the laboratory, which performed the UDS using
the EMIT II platform, was consulted. Confirmatory testing revealed that both urine
drug screens were falsely positive.
Analytes Cutoff
EMIT II (Syva)
Triage (Biosite)
(EMIT II)
(Triage)
Ranitidine
Chlorpromazine*
Bupropion*
Oxaprozin
Pantoprazole
Ofloxacin
Levofloxacin
Dextromethorphan
Dextrophan
Mesoridazine
Cyclobenzaprine

Table: Possible Interferents in Two Common Urine Drug of Abuse Assays.
The calibrator cutoff options for both the EMIT II plus and the Triage are listed.
Note that the medications listed above are potential interferents and will not
cross-react in all patients. Results must be interpreted in conjunction with the
clinical impression result and confirmatory testing results.
• *In some instances, a metabolite, not the parent compound, is causing
NewsPath® Editor: Megan J. DiFurio, MD, FCAP This newsletter is produced in cooperation with the College of American Pathologists’ Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright 2006
Scenario 1 (Answer): The 60-year-old male was taking ranitidine for his
gastroesophageal reflux disease, which cross-reacts in the EMIT amphetamine
assay.
Scenario 2 (Answer): The 80-year-old woman was prescribed levofloxacin for
pneumonia, which interferes with the EMIT opiate assay.
References
1. Hammett-Stabler CA, Pesce AJ, Cannon DJ. Urine drug screening in the medical setting. Clin Chim Acta. 2002;315:125-135. 2. Colbert DL. Drug abuse screening with immunoassays: unexpected cross-reactivity and other pitfalls. Br J Biomed Sci. 1994;51:136-146. 3. Magnani B. Concentrations of compounds that produce positive results. In: Shaw LM, Kwong TC, Rosano TG, Orsulak PJ, Wolf BA, Magnani B, eds. The Clinical Toxicology Laboratory: Contemporary Practice of Poisoning Evaluation. Washington, DC: AACC Press; 2001:481-498. 4. Product Information EMIT II Assay. Syva Company, San Jose, Calif. 5. Product Information Triage Drugs of Abuse Panel. Biosite Inc., San Diego, Calif. 6. Smith-Kielland A, Olsen KM, Christopherson AS. False-positive results with EMIT II amphetamine/methamphetamine assays in users of common psychotropic drugs. Clin Chem. 1995;41:951-952. 7. Nixon AL, Long WH, Puopolo PR. Flood JG. Bupropion metabolites produce false- positive urine amphetamine results. Clin Chem. 1995;41:955-956. NewsPath® Editor: Megan J. DiFurio, MD, FCAP This newsletter is produced in cooperation with the College of American Pathologists’ Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright 2006

Source: http://www.cap.org/apps/docs/newspath/0601/0601_NewsPath-UDS_False_Positives.pdf