Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate
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Otros documentos de la autoría: Pozo, Óscar J.; Ibáñez, Maria; Sancho, Juan V; Lahoz-Beneytez, Julio; Farré, Magi; Papaseit, Esther; De la Torre, Rafael; Hernandez, Felix
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Título
Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl ConjugateAutoría
Fecha de publicación
2015-02Editor
American Society for Pharmacology and Experimental Therapeutics (ASPET)ISSN
0090-9556; 1521-009XTipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://dmd.aspetjournals.org/content/43/2/248.fullVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
In recent years, many new designer drugs have emerged, including the group of cathinone derivatives. One frequently occurring drug is mephedrone; although mephedrone was originally considered as a “legal high” product, ... [+]
In recent years, many new designer drugs have emerged, including the group of cathinone derivatives. One frequently occurring drug is mephedrone; although mephedrone was originally considered as a “legal high” product, it is currently banned in most Western countries. Despite the banning, abuse of the drug and seizures are continuously reported. Although the metabolism of mephedrone has been studied in rats or in vitro using human liver microsomes, to the best of our knowledge, no dedicated study with human volunteers has been performed for studying the in vivo metabolism of mephedrone in humans. Therefore, the aim of this study was to establish the actual human metabolism of mephedrone and to compare it with other models. For this purpose, urine samples of two healthy volunteers, who ingested 200 mg mephedrone orally, were taken before administration and 4 hours after substance intake. The discovery and identification of the phase I and phase II metabolites of mephedrone were based on ultra-high-performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry, operating in the so-called MSE mode. Six phase I metabolites and four phase II metabolites were identified, four of them not previously reported in the literature. The structure of four of the detected metabolites was confirmed by synthesis of the suggested compounds. Remarkably, a mephedrone metabolite conjugated with succinic acid has been identified and confirmed by synthesis. According to the reviewed literature, this is the first time that this type of conjugate is reported for human metabolism. [-]
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Drug Metabolism and Disposition, 2015, vol. 43, no 2, p. 248-257Derechos de acceso
Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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info:eu-repo/semantics/openAccess
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