Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs ('Ecstasy').
The phase I and II metabolites of the designer drugs methylenedioxyamphetamine (MDA), R,S-methylenedioxymethamphetamine (MDMA), R,S-methylenedioxyethylamphetamine (MDE), 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: (1) 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.
Maurer
H H
HH
Department of Toxicology, Institute of Pharmacology, University of Saarland, D-66421, Homburg, Germany. hans.maurer@med.rz.uni.sb.de
Bickeboeller-Friedrich
J
J
Kraemer
T
T
Peters
F T
FT
D000662:Amphetamines / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid; D015198:Designer Drugs / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D000662:Amphetamines; D015198:Designer Drugs; D018817:N-Methyl-3,4-methylenedioxyamphetamine