Pozo Óscar J, Ibáñez María, Sancho Juan V, Lahoz-Beneytez Julio, Farré Magí, Papaseit Esther, de la Torre Rafael, Hernández Félix
Bioanalysis Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Hospital del Mar Medical Research Institute, Barcelona, Spain (O.J.P.); Research Institute for Pesticides and Water, University Jaume I, Castellón, Spain (M.I., J.V.S., F.H.); Human Pharmacology and Clinical Neurosciences Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona and Universitat Pompeu Fabra, Barcelona, Spain (J.L.-B., M.F., E.P., R.d.l.T.); and Warwick Systems Biology Centre, University of Warwick, Coventry, United Kingdom (J.L.-B.).
Bioanalysis Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Hospital del Mar Medical Research Institute, Barcelona, Spain (O.J.P.); Research Institute for Pesticides and Water, University Jaume I, Castellón, Spain (M.I., J.V.S., F.H.); Human Pharmacology and Clinical Neurosciences Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona and Universitat Pompeu Fabra, Barcelona, Spain (J.L.-B., M.F., E.P., R.d.l.T.); and Warwick Systems Biology Centre, University of Warwick, Coventry, United Kingdom (J.L.-B.)
Drug Metab Dispos. 2015 Feb;43(2):248-57. doi: 10.1124/dmd.114.061416. Epub 2014 Dec 2.
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 MS(E) 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.
近年来，出现了许多新型设计药物，包括卡西酮衍生物类。一种常见的药物是4-甲基甲卡西酮；尽管4-甲基甲卡西酮最初被视为一种“合法兴奋剂”产品，但目前在大多数西方国家已被禁用。尽管被禁，但该药物的滥用和缉获情况仍不断被报道。虽然已经在大鼠身上或使用人肝微粒体进行了体外研究4-甲基甲卡西酮的代谢，但据我们所知，尚未进行专门针对人类志愿者的研究来探究4-甲基甲卡西酮在人体内的体内代谢情况。因此，本研究的目的是确定4-甲基甲卡西酮在人体中的实际代谢情况，并将其与其他模型进行比较。为此，采集了两名健康志愿者口服200毫克4-甲基甲卡西酮之前和摄入药物4小时后的尿液样本。4-甲基甲卡西酮I相和II相代谢物的发现与鉴定基于超高效液相色谱与混合四极杆飞行时间质谱联用，以所谓的MS(E)模式运行。鉴定出了六种I相代谢物和四种II相代谢物，其中四种此前未见文献报道。通过合成所建议的化合物，证实了四种检测到的代谢物的结构。值得注意的是，已鉴定并通过合成证实了一种与琥珀酸共轭的4-甲基甲卡西酮代谢物。根据综述文献，这是首次报道这种类型的共轭物用于人类代谢。
