期刊
TOXICOLOGY LETTERS
卷 112, 期 -, 页码 133-142出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0378-4274(99)00207-6
关键词
designer drugs; methylenedioxy amphetamines; toxicokinetics; metabolism; GC-MS analysis
类别
The phase I and II metabolites of the designer drugs methylenedioxyamphetamine (MDA), R,S-methylenedioxymethamphetamine (MDMA), li,S-methylenedioxyethylamphetamine (NIDE), R,S-benzodioxazolylbutanamine (BDB) and R,S-N-methyl-benzodioxazolylbutanamine (MBDB) were identified by gas chromatography-mass spectrometry (GC-MS) or liquid chromotography-mass spectrometry (LC-MS) in urine and liver microsomes of humans and rats. Two overlapping pathways could be postulated: (I) demethylenation followed by catechol-O-methyl-transferase (COMT) catalyzed methylation and/or glucuronidation/sulfatation; (2) N-dealkylation, deamination and only for MDA, MDMA, MDE oxidation to the corresponding benzoic acid derivatives conjugated with glycine. Demethylenation was mainly catalyzed by CYP2D1/6 or CYP3A2/4, but also by CYP independent mechanisms. In humans, MDMA and MBDB could also be demethylenated by CYP1A2. N-demethylation was mainly catalyzed by CYP1A2, N-deethylation by CYP3A2/4. Based on these studies, GC-MS procedures were developed for the toxicological analysis in urine and plasma. Finally, toxicokinetic parameters are reviewed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
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