Stereospecific analysis and enantiomeric disposition of 3,4-methylenedioxymethamphetamine (Ecstasy) in humans

Background: Little is known concerning the enantioselective disposition of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) in humans. In addition, t he potential of utilizing the stereochemical composition of an analyte in b iological media for forensic purposes requires investigation. Methods: The enantiomers of MDMA and its demethylated metabolite, 3,4-methy lenedioxyamphetamine (MDA), present in plasma and urine extracts were deriv atized with (-)-(R)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chlorid e and analyzed by gas chromatography-mass spectrometry and gas chromatograp hy, respectively. The enantioselective disposition of MDMA and MDA was dete rmined following oral administration of racemic MDMA (40 mg) to eight male volunteers. Results: The plasma concentrations of (R)-MDMA exceeded those of the S-enan tiomer [ratio R:S of the area under the curve (AUC), 2.4 +/- 0.3], and the plasma half-life of (R)-MDMA (5.8 +/- 2.2 h) was significantly longer than that of the S-enantiomer (3.6 +/- 0.9 h). The majority of the recovered mat erial in urine was excreted within 24 h after dosing, with the recovery of (R)MDMA (21.4% +/- 11.6%) being significantly greater than that of (S)-MDMA (9.3% +/- 4.9%), and with (S)- and (R)-MDA accounting for 1.4% +/- 0.5% an d 1.0% +/- 0.3% of the dose, respectively. Mathematical modeling of plasma enantiomeric composition vs sampling time demonstrated the applicability of using stereochemical data for the prediction of time elapsed after drug ad ministration. Conclusions: Analytical methods for determining the enantiomeric compositio n of MDMA and MDA in plasma and urine were developed. The disposition of MD MA in humans is stereoselective, with the more active S-enantiomer having a reduced AUC and shorter half-life than (R)-MDMA. The determination of ster eochemical composition may be applicable for forensic purposes. (C) 1999 Am erican Association for Clinical Chemistry.