Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs ('Ecstasy')

Toxicol Lett. 2000 Mar 15:112-113:133-42. doi: 10.1016/s0378-4274(99)00207-6.

Abstract

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.

MeSH terms

  • Amphetamines* / metabolism
  • Amphetamines* / pharmacokinetics
  • Amphetamines* / toxicity
  • Animals
  • Area Under Curve
  • Chromatography, Liquid
  • Designer Drugs* / metabolism
  • Designer Drugs* / pharmacokinetics
  • Designer Drugs* / toxicity
  • Gas Chromatography-Mass Spectrometry
  • Half-Life
  • Humans
  • Liver / metabolism*
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / metabolism
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacokinetics
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity
  • Rats
  • Rats, Wistar
  • Species Specificity

Substances

  • Amphetamines
  • Designer Drugs
  • N-Methyl-3,4-methylenedioxyamphetamine