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Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans.
Clin Chem. 1999 Jul; 45(7):1058-69.CC

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

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Authors+Show Affiliations

Fallon JK
Drug Control Centre and Department of Pharmacy, King's College London, Manresa Road, London SW3 6LX, UK.
Kicman AT
No affiliation info available
Henry JA
No affiliation info available
Milligan PJ
No affiliation info available
Cowan DA
No affiliation info available
Hutt AJ
No affiliation info available

MeSH

Administration, OralAdultGas Chromatography-Mass SpectrometryHallucinogensHumansMaleN-Methyl-3,4-methylenedioxyamphetamineRegression AnalysisReproducibility of ResultsStereoisomerism

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

10388483

Citation

Fallon, J K., et al. "Stereospecific Analysis and Enantiomeric Disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in Humans." Clinical Chemistry, vol. 45, no. 7, 1999, pp. 1058-69.
Fallon JK, Kicman AT, Henry JA, et al. Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans. Clin Chem. 1999;45(7):1058-69.
Fallon, J. K., Kicman, A. T., Henry, J. A., Milligan, P. J., Cowan, D. A., & Hutt, A. J. (1999). Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans. Clinical Chemistry, 45(7), 1058-69.
Fallon JK, et al. Stereospecific Analysis and Enantiomeric Disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in Humans. Clin Chem. 1999;45(7):1058-69. PubMed PMID: 10388483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans. AU - Fallon,J K, AU - Kicman,A T, AU - Henry,J A, AU - Milligan,P J, AU - Cowan,D A, AU - Hutt,A J, PY - 1999/7/1/pubmed PY - 1999/7/1/medline PY - 1999/7/1/entrez SP - 1058 EP - 69 JF - Clinical chemistry JO - Clin Chem VL - 45 IS - 7 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 0009-9147 UR - https://www.unboundmedicine.com/medline/citation/10388483/Stereospecific_analysis_and_enantiomeric_disposition_of_3_4_methylenedioxymethamphetamine__Ecstasy__in_humans_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=10388483.ui DB - PRIME DP - Unbound Medicine ER -