Interference of metoprolol with amphetamines and MDMA immunoassays

Abstract

(1) To describe two cases of metoprolol intoxication with false positive urine drug screen for amphetamines and ecstasy. (2) To demonstrate cross-reactivity by doping urine samples with metoprolol and two phase I metabolites. A 30-year-old woman (case 1) was admitted to the intensive care unit (ICU) 7 h after the ingestion of sustained-release metoprolol (4 g) in a suicide attempt. Similarly, a 58-year-old woman (case 2) was admitted to the ICU 18 h following voluntary ingestion of sustained release metoprolol (5.4 g), lorazepam (32.5 mg) and dihydrocodeine (600 mg). Urine drug screen was realized on Architect C4000 ® (Abbott). Confirmation tests for positive results were carried out using GC-MS. Semi-quantitative plasma drug screen was performed with LC-DAD-MS. Metoprolol concentrations in plasma and urine were determined with liquid-chromatography coupled with fluorescence detection (LC-Fluo). In vitro experiments were conducted by diluting stock solutions of metoprolol, α -hydroxymetoprolol and O -demethylmetoprolol in blank urine at 200, 250, 500, 750 and 1000 μg/mL; cross-reactivity of each compound was then evaluated on an Architect C4000 ® instrument using MULTIGENT ® amphetamine/methamphetamine and MDMA kits. The urine drug screen was positive for amphetamines and MDMA in case 1 and positive for amphetamines, MDMA, opiates and buprenorphine in case 2. For both cases, confirmatory tests in urine were negative for amphetamine, metamphetamine, MDMA, MDA, MDEA, BDB, MBDB, phenylpropanolamine and ephedrine. LC-DAD-MS identified high plasma levels of metoprolol for both patients. The plasma metoprolol concentration measured by LC-Fluo on ICU admission was 5.9 μg/mL in case 1 and 6.9 μg/mL in case 2. Urinary concentration of metoprolol, only determined for case 1 on ICU admission, was 968 μg/mL. In vitro experiments in urine showed cross-reactivity between metoprolol and amphetamine/metamphetamine and between metoprolol and MDMA immunoassays at 200 and 150 μg/mL, respectively. In the same way, metoprolol phase I metabolites were shown to cross-react with amphetamine/metamphetamine test at 750 μg/mL for O -demethylmetoprolol and 2000 μg/mL for α -hydroxymetoprolol. However, no cross-reactivity was found between both metabolites and the MDMA kit. Urine drug screen are routinely performed in the poisoned patients admitted in the ICU because such assays are easy to perform and provide quick results. However, antibodies of immunoassays often lack of specificity and cross-react with related or unrelated compounds. We describe amphetamine and MDMA false positives in urine in 2 cases of metoprolol intoxication, with plasma concentrations above the therapeutic range (0.1–0.3 μg/mL). These two cases remind that interpretation of positive results obtained with automated amphetamines immunoassays should take into account the drug use history and systematically requires confirmation by mass spectrometry [1] . Moreover, interference should be demonstrated by in vitro experiment by doping urine samples not only with the parent compound but also with its major metabolites.