Pharmacokinetics of Mephedrone and Its Metabolites in Human by LC-MS/MS

被引:31
作者
Olesti, Eulalia [1 ,2 ]
Farre, Magi [3 ,4 ]
Papaseit, Esther [3 ,4 ]
Krotonoulas, Aristotelis [5 ]
Pujadas, Mitona [1 ,6 ]
de la Torre, Rafael [1 ,2 ,6 ]
Pozo, Oscar J. [1 ]
机构
[1] Hosp del Mar, Med Res Inst, Integrat Pharmacol & Syst Neurosci Res Grp, Neurosci Res Program,IMIM, Dr Aiguader 88, Barcelona 08003, Spain
[2] Pompeu Fabra Univ CEXS UPF, Dr Aiguader 88, Barcelona 08003, Spain
[3] Hosp Univ Germans Trias & Pujol IGTP, Dept Clin Pharmacol, Badalona, Spain
[4] Univ Autonoma Barcelona, Sch Med, Cerdanyola Del Valles, Spain
[5] Spanish Council Sci Res IQAC CSIC, Dept Biol Chem & Mol Modelling, Inst Adv Chem Catalonia, Jordi Girona 18-26, Barcelona 08034, Spain
[6] CIBEROBN, CIBER Fisiopatol Obesidad & Nutr CB06 03, Madrid, Spain
关键词
analytical method; LC-MS/MS; mephedrone; nor-mephedrone; pharmacokinetics; CHROMATOGRAPHY-MASS SPECTROMETRY; MONOAMINE TRANSPORTERS; SYNTHETIC CATHINONES; HUMAN PHARMACOLOGY; ORAL FLUID; PHASE-I; ANALOGS; URINE; MDMA; PHARMACODYNAMICS;
D O I
10.1208/s12248-017-0132-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N-succinyl-nor-mephedrone, 1'-dihydro-mephedrone, and 4'-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4'-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N-succinyl-nor-mephedrone was the metabolite eliminated with the longer half-life of 8.2 h. In urine, 4'-carboxy-mephedrone was the main metabolite excreted with amounts recovered being about 10 times those of mephedrone. Additionally, the validated method was used to test metabolite ability to cross the blood-brain barrier in vivo in rats with mephedrone and nor-mephedrone as the main active compounds present in the brain. The method described is useful for the determinations of mephedrone and metabolites in biological samples.
引用
收藏
页码:1767 / 1778
页数:12
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