近日,公安部禁毒情报技术中心胡文老师,使用IPHASE品牌产品:pHLMs在《Biomedical chromatography》权威期刊上发表文章《Metabolism of four novel structural analogs of ketamine, 2-FXE [2-(ethylamino)-2-(2-fluorophenyl) cyclohexan-1-one], 2-MDCK [2-(methylamino)-2-(o-tolyl) cyclohexan-1-one], 3-DMXE [2-(ethylamino)-2-(m-tolyl) cyclohexan-1-one], and 2-DMXE [2-(ethylamino)-2-(o-tolyl) cyclohexan-1-one], in human liver microsomes based on ultra-performance liquid chromatography–high-resolution tandem mass spectrometry》,影响因子1.8!
本论文中提到:新的精神活性物质不断涌现,其中具有2-氨基-2-苯基环己酮核心结构的氯胺酮类似物因其持续参与急性中毒而引起全球关注,这些物质的监测很大程度上依赖于代谢数据的获取,然而,缺乏这些新兴结构类似物的体外人类代谢信息给药物控制工作带来了重大挑战,为了应对这一挑战,研究了四种新型氯胺酮结构类似物的第一阶段代谢模式,首次利用人肝微粒体,使用超高效液相色谱法和高分辨率串联质谱法鉴定代谢物,研究结果表明,N-脱烷基化和羟基化是主要的代谢反应,还有其他显着的反应,包括氧化、还原和脱水。
摘要
New psychoactive substances are constantly emerging, among which ketamine analogs with the core structure of 2-amino-2-phenylcyclohexanone have attracted global attention due to their continued involvement in acute intoxications. The monitoring of these substances largely relies on the acquisition of metabolic data. However, the lack of in vitro human metabolism information for these emerging structural analogs presents significant challenges to drug control efforts. To address this challenge, we investigated the first-phase metabolism patterns of four novel ketamine structural analogs of 2-FXE [2-(ethylamino)-2-(2-fluorophenyl) cyclohexan-1-one], 2-MDCK [2-(methylamino)-2-(o-tolyl) cyclohexan-1-one], 3-DMXE [2-(ethylamino)-2-(m-tolyl) cyclohexan-1-one], and 2-DMXE [2-(ethylamino)-2-(o-tolyl) cyclohexan-1-one] utilizing human liver microsomes for the first time. Metabolites were identified using ultra-performance liquid chromatography coupled with high-resolution tandem mass spectrometry. Our findings reveal that N-dealkylation and hydroxylation are the primary metabolic reactions, alongside other notable reactions, including oxidation, reduction, and dehydration. Based on our extensive research, we propose Ndealkylation and hydroxylation metabolites as appropriate analytical markers for monitoring the consumption of these substances.
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