Stereoselective disposition: enantioselective quantitation of 3,4-(methylenedioxy) methamphetamine and three of its metabolites by gas chromatography/electron capture negative ion chemical ionization mass spectrometry.

A new chiral assay for 3,4-(methylenedioxy)methamphetamine (MDMA) and three of its metabolites in biological specimens is based on direct aqueous derivatization with N-heptafluorobutyryl-S-prolyl chloride, followed by capillary chromatographic separation of the diastereomeric derivatives and detection by a mass spectrometer operated in the electron capture negative ion chemical ionization mode. The assay is linear from 5 to 1000 ng ml-1 for each enantiomer and allows simultaneous quantitation of MDMA and three of its metabolites in biological specimens. Investigation of the disposition of racemic MDMA in rats and mice revealed quantitative differences in the disposition of the enantiomers of MDMA in these species; the most noteworthy result was a two-fold greater urinary excretion of the neurotoxic S-(+)-MDMA by mice. Only MDMA and 3,4-(methylenedioxy)amphetamine (MDA) enantiomers were detected at measurable concentrations in the frontal cortices and hippocampis from rats dosed with 10 mg kg-1 of racemic MDMA; in this species the enantiomeric profiles of these two compounds were similar in brain and urine.