Determination of a new designer drug, N-hydroxy-3,4-methylenedioxymethamphetamine and its metabolites in rats using ultra-performance liquid chromatography-tandem mass spectrometry

Forensic Sci Int. 2010 May 20;198(1-3):62-9. doi: 10.1016/j.forsciint.2010.02.013. Epub 2010 Mar 17.

Abstract

An N-hydroxy analogue of 3,4-methylendioxymethamphetamine (MDMA), N-hydroxy MDMA (N-OH MDMA), has recently been distributed as a new designer drug in some drug markets. Very little data is available to the metabolic and pharmacological properties of N-OH MDMA, although it has been reported that the N-demethyl analogue, N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), is mainly metabolized to MDA in rats. In this study, an analytical method for the determination of N-OH MDMA and its metabolites in biological samples was developed, and the metabolic properties of N-OH MDMA in rats were investigated. After the i.p. administration of N-OH MDMA to pigmented hairy rats (5mg/kg/day, 10 days), N-OH MDMA and its N-dehydroxy and N-demethyl metabolites (MDMA, N-OH MDA and MDA) in rat plasma, urine and hair samples were determined by ultra-performance LC (UPLC)-MS/MS. The hair sample was extracted by 1-h sonication and overnight soaking in 5M hydrochloric acid-methanol (1:20). The plasma, urine, and hair extract samples were purified using a solid-phase extraction procedure. N-OH MDMA in the samples could be precisely analyzed by avoiding an alkaline environment. The parent compound very rapidly disappeared from the rat plasma (<15min) and urine (<10h), and most of the N-OH MDMA was excreted in the rat urine as MDMA and MDA in 72h. In the rat hair samples collected 4 weeks after the first administration, N-OH MDMA (0.03ng/mg) and N-OH MDA (0.13ng/mg) were clearly detected as well as MDMA (149ng/mg) and MDA (52ng/mg). This analytical method will be useful for the analysis of N-OH MDMA and its metabolites in biological samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives*
  • 3,4-Methylenedioxyamphetamine / analysis
  • Animals
  • Chromatography, Liquid
  • Designer Drugs / analysis*
  • Forensic Toxicology
  • Hair / chemistry
  • Hallucinogens / analysis*
  • Male
  • Rats
  • Tandem Mass Spectrometry

Substances

  • Designer Drugs
  • Hallucinogens
  • 3,4-Methylenedioxyamphetamine
  • N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane