A gas chromatography-mass spectrometry method simultaneously measured MDMA and its metabolites MDA, HMMA, and HMA in plasma and urine from healthy volunteers given 100 mg of MDMA. Samples were hydrolyzed, extracted with solid-phase columns, and analyzed as trifluoroacyl derivatives. Linear calibration covered plasma and urine ranges of 25–400 ng/mL and 250–2000 ng/mL for MDMA and HMMA, and 2.5–40 ng/mL and 100–1000 ng/mL for MDA and HMA. A capillary electrophoresis method using (2-hydroxy)propyl-beta-cyclodextrin as chiral selector resolved enantiomers without derivatization, with linear ranges for each enantiomer of MDMA, MDA, and HMMA. Stereoselective disposition of MDMA and MDA was confirmed, while HMMA showed an enantiomer ratio near 1 and constant over time, contradicting MDMA findings.
A new method using strong cation-exchange solid-phase extraction and high-performance liquid chromatography with electrochemical detection was validated for measuring the metabolite 3,4-dihydroxymethamphetamine (HHMA) in plasma and urine. Applied to samples from healthy volunteers given MDMA (ecstasy), HHMA appeared as a major metabolite, with peak plasma concentrations (154.5 microg/L) and overall exposure (AUC 1990.9 microg/L h) similar to those of MDMA itself. Urinary recovery of HHMA over 24 hours accounted for 17.7% of the 100 mg MDMA dose, raising total recovery of MDMA and its metabolites to 58%. The method is accurate and precise for pharmacokinetic studies, and measuring HHMA may help clarify its role in MDMA metabolism and potential neurotoxicity.