MDMA and Metabolite Disposition in Expectorated Oral Fluid After Controlled Oral MDMA Administration

Introduction: The use of 3,4-methylenedioxymethamphetamine (MDMA) is increasing, enhancing the need for its detection in clinical, workplace, pain management, and driving under the influence of drugs testing programs. Oral fluid is an important alternative matrix for drug testing, but little is known about MDMA detection windows in oral fluid. Aims: The aim was to characterize MDMA and metabolite disposition in expectorated oral fluid after controlled MDMA administration. Methods: Placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral MDMA doses were given double-blind in random order in separate sessions to 29 healthy adults with histories of MDMA use. One thousand two hundred eighty-six expectorated oral fluid specimens collected up to 7 days after dosing were analyzed for MDMA, 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) by gas chromatography mass spectrometry. The limits of quantification were 5 ng/mL for MDMA and MDA and 10 ng/mL for HMA and HMMA. Results: MDMA was the primary analyte detected, with concentrations up to 12,000 ng/mL in 872 specimens (67.8%). MDA was quantified in 656 specimens (51.0%) at concentrations,403 ng/mL and was never present without concurrent MDMA. HMA and HMMA were not detected. Of the specimens, 59.8%, 58.6%, and 54.9% were found to be MDMA positive at the Talloires (20 ng/mL), Driving under the Influence of Drugs, Alcohol, and Medicines (25 ng/mL) and proposed US Substance Abuse and Mental Health Services Administration (50 ng/mL) confirmation cutoffs, respectively. MDMA was first observed in oral fluid 0.25-1.25 hours after dosing; MDA was initially detected at 0.5-1.75 hours. In general, the windows of detection for MDMA and MDA were 47 and 29 hours, respectively, although a few specimens were positive up to 71 and 47 hours. Conclusions: Oral fluid monitoring efficiently detects single, recreational 70-150 mg of MDMA use for 1-2 days. These controlled administration data provide a scientific basis for interpreting MDMA oral fluid test results.