近日,公安部禁毒情报技术中心李静老师,使用IPHASE品牌产品:人肝微粒体在《Biomedical Chromatography》权威期刊上发表文章《UPLC-HR-MS/MS-based determination study on the metabolism of four synthetic microsomes cannabinoids ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA, by human liver》,影响因子1.8!
本论文中提到:自2012年以来,非法药物市场上出现了几种带有缬氨基酸酰胺残留的大麻模拟吲唑和吲哚衍生物,并逐渐用萘基或金刚烷基团,取代了老一代合成大麻素(SCs)。其中,ADB-FUBICA、AB-FUBICA、AB-BICA 和 ADB-BICA 最近在国内被发现,但遗憾的是,目前尚无关于其体外人体代谢的信息。因此,筛选其消费的生物监测研究缺乏有关潜在生物标志物(例如代谢物)的任何信息,为了弥合这一差距,通过与人肝微粒体孵育来研究它们的I期代谢,并通过超高效液相色谱-高分辨率串联质谱(UPLC-HR-MS/MS)鉴定代谢物,发现1-氨基烷基部分的N-脱烷基化和羟基化产生的代谢物对这四种物质均占主导地位,其他经过羟基化、酰胺水解和脱氢的代谢物也在研究中被观察到,根据研究,建议N-脱烷基化和羟基化代谢物是监测其摄入量的合适和适当的分析标志物。
摘要
Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA were detected in China recently, but unfortunately no information about their in vitro human metabolism is available for now. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g.metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by Ultra Performance liquid chromatography-high resolution-tandem mass spectrometry (UPLC-HR-MS/MS). Metabolites generated by N-dealkylation and hydroxylation on the 1-amino-alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N-dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake.
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