ON THE METABOLISM AND THE TOXICOLOGICAL ANALYSIS OF METHYLENEDIOXYPHENYLALKYLAMINE DESIGNER DRUGS BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

Designer drugs of the methylenedioxyphenylalkylamine type are increasi ngly abused. Studies on their metabolism in humans are necessary to de velop a reliable gas chromatography-mass spectrometry (GC-MS) screenin g procedure. Such a method must allow their detection in urine for dru g testing in clinical and forensic toxicology. Studies on racemic meth ylenedioxyamphetamine (MDA), methylenedioxymetamphetamine (MDMA), meth ylenedioxyethylamphetamine (MDE), benzodioxazolylbutanamine (BDB), and N-methyl-benzodioxazolylbutanamine (MBDB) are presented. The metaboli tes were identified by GC-MS after enzymatic hydrolysis, isolation (pH 4.5 and 8-9), and derivatization (acetylation followed by methylation ). The drugs undergo two overlapping metabolic pathways: O-dealkylatio n of the methylenedioxy group to dihydroxy derivatives followed by met hylation of one of the hydroxy groups and successive degradation of th e side chain to N-dealkyl and deaminooxo metabolites. MDA, MDMA, and M DE are subsequently metabolized to glycine conjugates of the correspon ding 3,4-disubstituted benzoic acids. The hydroxy metabolites are excr eted in a conjugated form. Based on these results, a GC-MS procedure w as developed for simultaneous screening and identification of these de signer drugs and/or their metabolites in urine after acid hydrolysis, isolation at pH 8-9, and acetylation. With use of mass chromatography with the most characteristic fragment ions mit 58, 72, 86, 150, 162, 1 64, 176, and 178, the presence of the designer drugs was indicated and the peak underlying spectra could be identified by computerized compa rison with reference spectra recorded during the presented studies. Th e procedure was suitable to detect an abuse of or an intoxication with the studied designer drugs (detection limit 5-50 ng/ml).