Determination of 4-hydroxy-3-methoxymethamphetamine as a metabolite of methamphetamine in rats and human liver microsomes using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry

J Anal Toxicol. 2009 Jun;33(5):266-71. doi: 10.1093/jat/33.5.266.


The aim of this study was to determine whether methamphetamine (MA) is metabolized to 4-hydroxy-3-methoxymethamphetamine (HMMA), which is known as the main metabolite of 3,4-methylenedioxymethamphetamine (MDMA). After MA was intravenously administered to rats, the plasma, urine, and bile were collected periodically. HMMA together with MA and its main metabolites, amphetamine and 4-hydroxymethamphetamine, were detected in the rat plasma, urine, and bile by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. In addition, HMMA was produced when MA was incubated with human liver microsomes. HMMA may be produced as a metabolite of MA when humans have consumed MA, although the amount of HMMA would be small compared with that of MA, amphetamine, or 4-hydroxymethamphetamine. The results of the present study will be helpful in determining the type of drug used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / analysis
  • Amphetamine / metabolism
  • Animals
  • Bile / chemistry
  • Chromatography, High Pressure Liquid
  • Gas Chromatography-Mass Spectrometry / methods*
  • Humans
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / analysis
  • Methamphetamine / metabolism
  • Methamphetamine / pharmacokinetics*
  • Microsomes, Liver / chemistry
  • Microsomes, Liver / metabolism*
  • Rats
  • Rats, Wistar
  • Tandem Mass Spectrometry / methods*


  • 4-hydroxy-3-methoxymethamphetamine
  • Methamphetamine
  • Amphetamine