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
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
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.
|EMIT II (Syva)
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 interference.
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.
- Hammett-Stabler CA , Pesce AJ, Cannon DJ. Urine
drug screening in the medical setting. Clin Chim Acta. 2002;315:125-135.
- Colbert DL. Drug abuse screening with immunoassays:
unexpected cross-reactivity and other pitfalls. Br J Biomed Sci.
- 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;
- Product Information EMIT II Assay. Syva Company,
San Jose , Calif.
- Product Information Triage Drugs of Abuse Panel.
Biosite Inc., San Diego , Calif.
- 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.
- Nixon AL , Long WH, Puopolo PR. Flood JG. Bupropion
metabolites produce false-positive urine amphetamine results. Clin
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