Reduced Interference by Phenothiazines in Amphetamine Drug of Abuse Immunoassays

Archives of Pathology & Laboratory Medicine,  Dec 2006  by Melanson, Stacy E F,  Lee-Lewandrowski, Elizabeth,  Griggs, David A,  Long, William H,  Flood, James G

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Context.-Emergency department physicians frequently request urine drug screens, but many are unaware of their limitations, including the potential for false-positive results. Promethazine, a phenothiazine derivative, is used for the treatment of allergies, agitation, nausea, and vomiting. Many patients taking promethazine are subject to urine drug screens and any potential interferences are important to recognize.

Design.-During an 11-month period, all patients presenting to the Massachusetts General Hospital emergency department who had a finding of promethazine in their serum drug screen, and who also had a urine drug screen performed, were selected for inclusion in the study. The urine drug screen results (n = 22 patients/samples) were then studied.

Objective.-To determine if promethazine use can cause false-positive urine amphetamine results in widely used drug of abuse immunoassays.

Results.-Thirty-six percent of patients taking promethazine had false-positive test results for urine amphetamines using the EMIT II Plus Monoclonal Amphetamine/Methamphetamine Immunoassay. Sixty-four percent of patients showed cross-reactivity greater than 20% higher than the blank calibrator rate. In a separate, related study, no promethazine- induced false-positive results were seen with the EMIT II Plus, Triage, and TesTcard 9 amphetamine assays, or the Triage methamphetamine assay. Reduced chlorpromazine interference was also seen with these other assays.

Conclusions.-False-positive urine amphetamine results can be obtained in patients taking promethazine. Promethazine metabolite(s), and not the parent compound, are the likely cause of these urine false-positive results obtained with EMIT II Plus Monoclonal Amphetamine/Methamphetamine Immunoassay. Immunoassays from different manufacturers can have very different "interference" profiles, which the pathologist and laboratory scientist must understand and relay to clinicians.

(Arch Pathol Lab Med. 2006;130:1834-1838)

Immunoassays are frequently employed for urine screening for drugs of abuse because they are simple, easily automated, and available in point-of-care testing format.1 However, there are some disadvantages to immunoassays. The earlier version of the monoclonal enzyme multiplied immunoassay technique (EMIT), EMIT dau (Syva Corp, Palo Alto, Calif) amphetamine assay, provided frequent false-positive results caused by phenylpropanolamine, ranitidine, chlorpromazine, and other medications.2-4 Falsepositive results can be challenging and expensive for a laboratory. In addition, confirmatory analysis of either positive or negative results may be necessary in certain clinical situations. Many immunoassay platforms for drug detection are available, and the specificity and sensitivity for detection of use of a particular drug can vary greatly depending on which manufacturer's assay is used, and which drug within a class is to be detected. A platform should be chosen that most accurately detects the drugs abused by the laboratory's patient population. Clinicians are frequently unaware of the limitations of urine drug screens, and inaccurate interpretation of results can adversely affect patient management. Furthermore, a stigma is attached to patients who have positive test results in the types of tests used to detect drugs of abuse.

In 1993 a new assay was developed, the EMIT II Monoclonal Amphetamine/Methamphetamine (EMIT-MAM) immunoassay (Syva Corp), which reportedly had a higher specificity for amphetamines and methamphetamines. Despite the improved specificity, the EMIT-MAM still provided some false-positive amphetamine results caused by certain classes of medications such as antipsychotics and antihistamines.3 Studies have demonstrated that chlorpromazine or bupropion use can cause a false-positive result. 4,5 Importantly, chlorpromazine metabolite(s), not the parent drug, were shown to cause the interference.4 The EMIT-MAM assay was also shown to be more sensitive to bupropion metabolites than the parent compound.5 Only certain compounds have been tested for cross-reactivity, and the manufacturer provides a list of these in the package insert. Many compounds and their metabolites are not screened for potential cross-reactivity, which makes it im- portant for clinical laboratories to report any new observations.

Data from our toxicology laboratory reveal that many patients taking promethazine also have 'amphetamine' detected in their urine, even though the patient denies taking any form of amphetamine. We investigate the validity of these amphetamine results in an attempt to determine any interference of promethazine in the EMIT-MAM assay. Finally, we report results of 6 different test systems on urine samples from patients ingesting promethazine or chlorpromazine.

MATERIALS AND METHODS

We identified all patients presenting to the emergency department during an 11-month period who had promethazine detected in their serum toxicology screen and who also had a urine toxicology screen performed. If promethazine was detected in a patient' serum, we then used the laboratory information system to retrospectively identify those patients who also had an EMITMAM urine toxicology screen performed at the same time as their serum analysis. All patients with promethazine detected in their serum and who also had an EMIT-MAM urine toxicology screen, regardless of the results, were included in the study (n = 22). Results of the EMIT-MAM drug screen were obtained from the laboratory information system and used in the data analysis.