Stereospecific Analysis and Enantiomeric Disposition of 3,4-Methylenedioxymethamphetamine (Ecstasy) in Humans

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 1999-07, Vol.45 (7), p.1058-1069
• Main Authors: Fallon, John K, Kicman, Andrew T, Henry, John A, Milligan, Peter J, Cowan, David A, Hutt, Andrew J
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Biological and medical sciences; Drug addictions; Gas Chromatography-Mass Spectrometry; Hallucinogens - blood; Hallucinogens - pharmacokinetics; Hallucinogens - urine; Humans; Male; Medical sciences; N-Methyl-3,4-methylenedioxyamphetamine - blood; N-Methyl-3,4-methylenedioxyamphetamine - pharmacokinetics; N-Methyl-3,4-methylenedioxyamphetamine - urine; Neuropharmacology; Pharmacology. Drug treatments; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Regression Analysis; Reproducibility of Results; Stereoisomerism; Toxicology
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/45.7.1058

Little is known concerning the enantioselective disposition of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) in humans. In addition, the potential of utilizing the stereochemical composition of an analyte in biological media for forensic purposes requires investigation. The enantiomers of MDMA and its demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), present in plasma and urine extracts were derivatized with (-)-(R)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride and analyzed by gas chromatography-mass spectrometry and gas chromatography, respectively. The enantioselective disposition of MDMA and MDA was determined following oral administration of racemic MDMA (40 mg) to eight male volunteers. The plasma concentrations of (R)-MDMA exceeded those of the S-enantiomer [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 material 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% and 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 administration. Analytical methods for determining the enantiomeric composition of MDMA and MDA in plasma and urine were developed. The disposition of MDMA in humans is stereoselective, with the more active S-enantiomer having a reduced AUC and shorter half-life than (R)-MDMA. The determination of stereochemical composition may be applicable for forensic purposes.