Hydrolysis of 3,4-methylenedioxymethamphetamine (MDMA) metabolite conjugates in human, squirrel monkey, and rat plasma

Melanie Mueller, Erin A. Kolbrich-Spargo, Frank T. Peters, Marilyn A. Huestis, George A. Ricaurte, Hans H. Maurer

Research output: Contribution to journalArticlepeer-review

Abstract

Characterizing the formation of metabolites of 3,4- methylenedioxymethamphetamine (MDMA, "Ecstasy") in different species (rat, squirrel monkey, and human) may provide insight into mechanisms of MDMA neurotoxicity. Two prominent MDMA metabolites, 3,4-dihydroxymethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), are conjugated with glucuronic or sulfuric acid, but reference standards are not available; therefore, quantification is only possible after conjugate cleavage. Different concentrations of HHMA and HMMA were obtained in human, squirrel monkey, and rat plasma specimens when acid or enzymatic cleavage was performed. Our data document that these differences are due to species-specific influences on conjugate cleavage. Acidic hydrolysis should be used for analyzing free HHMA and HMMA in human or squirrel monkey plasma, while enzymatic hydrolysis with glucuronidase or sulfatase maximizes recovery of free HHMA and HMMA in rat plasma. Optimization of cleavage conditions showed that sulfate conjugates were more readily cleaved by acid hydrolysis and glucuronides by glucuronidase.

Original languageEnglish (US)
Pages (from-to)1607-1617
Number of pages11
JournalAnalytical and Bioanalytical Chemistry
Volume393
Issue number6-7
DOIs
StatePublished - Mar 1 2009

Keywords

  • Human
  • Hydrolysis
  • LC-ESI-MS
  • MDMA
  • Metabolites
  • Plasma
  • Rat
  • Squirrel monkey

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

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