Hydrolysis of 3,4-methylenedioxymethamphetamine (MDMA) metabolite conjugates in human, squirrel monkey, and rat plasma
- 30 January 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Analytical and Bioanalytical Chemistry
- Vol. 393 (6), 1607-1617
- https://doi.org/10.1007/s00216-009-2607-1
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.Keywords
This publication has 40 references indexed in Scilit:
- Simultaneous liquid chromatographic-electrospray ionization mass spectrometric quantification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and its metabolites 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine and 3,4-methylenedioxyamphetamine in squirrel monkey and human plasma after acidic conjugate cleavageForensic Science International, 2009
- The Role of Human Hepatic Cytochrome P450 Isozymes in the Metabolism of Racemic 3,4-Methylenedioxy-Methamphetamine and Its EnantiomersDrug Metabolism and Disposition, 2008
- Urinary excretion of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and ratsXenobiotica, 2008
- Two-Dimensional Gas Chromatography/Electron-Impact Mass Spectrometry with Cryofocusing for Simultaneous Quantification of MDMA, MDA, HMMA, HMA, and MDEA in Human PlasmaClinical Chemistry, 2008
- Validated liquid chromatographic–electrospray ionization mass spectrometric assay for simultaneous determination of 3,4-methylenedioxymethamphetamine and its metabolites 3,4-methylenedioxyamphetamine, 3,4-dihydroxymethamphetamine, and 4-hydroxy-3-methoxymethamphetamine in squirrel monkey plasmaJournal of Chromatography B, 2007
- Ecstasy: Are animal data consistent between species and can they translate to humans?Journal of Psychopharmacology, 2006
- Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humansTrends in Pharmacological Sciences, 2004
- Human Pharmacology of MDMATherapeutic Drug Monitoring, 2004
- Species differences in the metabolism of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amineCarcinogenesis: Integrative Cancer Research, 1987
- Preparative isolation and purification of urinary conjugates in antipyrine metabolism in man and ratNaunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1982