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Rapid Urine Drug Screens: Diphenhydramine and Methadone Cross-Reactivity

Rogers, Steven C. MD*; Pruitt, Charles W. MD; Crouch, Dennis J. BS, MBA; Caravati, E. Martin MD

doi: 10.1097/PEC.0b013e3181f05443
Illustrative Cases

Background: Rapid urine screens to detect drugs of abuse are often used in pediatric emergency departments (PEDs). A positive result may lead to further clinical testing, social evaluation, and increased stress/inconvenience. A PED patient with suspected diphenhydramine (DPH) ingestion had a positive methadone result on the rapid urine drug screen, One Step Multi-Drug, Multi-Line Screen Test Device (ACON Laboratories, San Diego, Calif). There was no history of methadone exposure so the patient was admitted while confirmatory testing was performed. Gas chromatography/mass spectroscopy testing of the urine failed to confirm the presence of methadone. We present this unreported false-positive methadone result and evaluation of the kit for cross-reactivity of DPH and methadone.

Methods: The same One Step urine drug screen was tested at an independent laboratory for cross-reactivity between methadone and DPH including the DPH metabolites. Drug-free urine was fortified with DPH, nordiphenhydramine, or dinordiphenhydramine at 0, 10, 25, 50, and 100 μg/mL for each analyte. One hundred microliters of the solutions were added to each of the 4 wells on test cassettes. Urine was allowed to migrate according to manufacturer instructions. Each cassette was interpreted by 2 analysts to ensure consistent interpretation and accurate data recording.

Results: In vitro laboratory testing results showed cross-reactivity between methadone and DPH but not for nordiphenhydramine or dinordiphenhydramine.

Conclusions: Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for patients who have ingested DPH. Product information for urine drug screens may not include all cross-reacting agents and should be used with caution when interpreting drug screen results in PED patients.

From the *Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, CT; †University of Utah School of Medicine,Salt Lake City, UT; and ‡Sports Testing, Aegis Sciences Corporation, Nashville, TN.

Reprints: Steven C. Rogers, MD, Connecticut Children's Medical Center, University of Connecticut School of Medicine, 282 Washington St, Hartford, CT 06106 (e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.