Steuer, Andrea E. and Schmidhauser, Corina and Liechti, Matthias E. and Kraemer, Thomas. (2015) Development and validation of an LC-MS/MS method after chiral derivatization for the simultaneous stereoselective determination of methylenedioxy-methamphetamine (MDMA) and its phase I and II metabolites in human blood plasma. Drug testing and analysis, 7 (7). pp. 592-602.
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Abstract
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a racemic drug of abuse and its two enantiomers are known to differ in their dose-response curves. The S-enantiomer was shown to be eliminated at a higher rate than the R-enantiomer. The most likely explanation for this is a stereoselective metabolism also claimed in in vitro studies. Urinary excretion studies showed that the main metabolites in humans are 4-hydroxy 3-methoxymethamphetamine (HMMA) 4-sulfate, HMMA 4-glucuronide and 3,4-dihydroxymethamphetamine (DHMA) 3-sulfate. For stereoselective pharmacokinetic analysis of phase I and phase II metabolites in human blood plasma useful analytical methods are needed. Therefore the aim of the presented study was the development and validation of a stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of MDMA, 3,4-methylenedioxyamphetamine, DHMA, DHMA 3-sulfate, HMMA, HMMA 4-glucuronide, HMMA 4-sulfate, and 4-hydroxy 3-methoxyamphetamine in blood plasma for evaluation of the stereoselective pharmacokinetics in humans. Blood plasma samples were prepared by simple protein precipitation and afterwards all analytes were derivatized using N-(2,4-dinitro-5-fluorophenyl) L-valinamide resulting in the formation of diastereomers which were easily separable on standard reverse phase stationary phases. This simple and fast method was validated according to international guidelines including specificity, recovery, matrix effects, accuracy and precision, stabilities, and limits of quantification. The method proved to be selective, sensitive, accurate and precise for all tested analytes except for DHMA.
Faculties and Departments: | 03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie 03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Psychopharmacology Research (Liechti) |
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UniBasel Contributors: | Liechti, Matthias Emanuel |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Wiley |
ISSN: | 1942-7611 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Identification Number: |
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edoc DOI: | |
Last Modified: | 30 Jun 2016 11:03 |
Deposited On: | 21 Mar 2016 14:43 |
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