GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC ASSAY FOR PROFILING THE ENANTIOMERS OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE AND ITS CHIRAL METABOLITES USING POSITIVE CHEMICAL-IONIZATION ION-TRAP MASS-SPECTROMETRY

A qualitative GC/MS profile was obtained and its mass spectrometric fe atures characterized for the analysis of the enantiomers of (RS)-3-4-m ethylenedioxymethamphetamin (MDMA) and its metabolites (RS)-3,4-methle enedioxyamphetamine (ha)A), (RS)-4-hydroxy-3-methoxymethamphetamine (H MMA) and (RS)-4-hydroxy-3-methoxyamphetamine (HMA). A chiral derivatiz ation method was selected to obtain the diastereomers required for the separation of the respective enantiomers with a non-chiral GC station ary phase, The selected derivatization consisted of a reaction with N- heptafluorobutyryl-(S)-prolyl chloride combined with a consecutive rea ction with N-methyl-N-trimethylsilyltrifluoroacetamide, resulting in N -[heptafluorobutyryl-(S)-prolyl]-O-trimethylsilyl derivatives, Detecti on was carried out with electron ionization and positive chemical ioni zation (PCI) ion trap mass spectrometry, Mass spectra of the derivativ es of reference standards of the compounds of interest obtained with P CI demonstrated that this method simultaneously induces proton and cha rge-transfer reactions in the ion trap. The advantage is that high mas s information is provided while some fragmentation remains to elucidat e structural details, Subsequently; in three urine samples obtained fr om different and unrelated MDMA intoxications, the enantiomers of MDMA and MDA were identified. In some urine samples also HMMA and/or HMA w ere found, In addition to these compounds, an unexpected compound and/ or additional chiral metabolite, N-hydroxy-(RS)-3,4-methylenedioxyamph etamine, was identified in two out of three urine samples, Preliminary results also indicated an enantioselective metabolism in the N-demeth ylation pathway for MDMA in humans. (C) 1997 John Wiley & Sons, Ltd.