苯乙胺类新精神活性物质2C-B-FLY和25B-NBOH的体外代谢研究

Study on metabolism of phenethylamines new psychoactive substances 2C-B-FLY and 25B-NBOH in vitro

目的 探究苯乙胺类新精神活性物质2C-B-FLY和25B-NBOH在人肝微粒体中的体外代谢产物及代谢途径。方法 建立人肝微粒体孵育模型,样品在37℃水浴共孵育3 h后离心、吹干、复溶,用超高效液相色谱-Q Exactive质谱ESI~+模式对样品进行检测,运用Full scan-ddMS^(2)数据依赖型采集模式对母药及其代谢产物进行检测。结果 经人肝微粒体体外孵育实验,2C-B-FLY经代谢共产生4种Ⅰ相代谢物和1种乙酰化的Ⅱ相代谢物,发生了羟基化、去溴化、N-乙酰化等代谢反应。25B-NBOH经代谢共产生8种Ⅰ相代谢物和2种葡萄糖醛酸化的Ⅱ相代谢物,包括的主要生物转化反应为O-去甲基化、羟基化、胺基脱氢、N-脱烷基化和葡萄糖醛酸化。结论 本研究阐述了2C-B-FLY和25B-NBOH在人肝微粒体孵育体系中的代谢产物及代谢途径,为苯乙胺类新精神活性物质的体内检测提供科学依据。

Objective To investigate the in vitro metabolites and metabolic pathways of phenethylamine new psychoactive substances 2C-B-FLY and 25B-NBOH in human liver microsomes.Methods The human liver microsome incubation model was established,and the samples were centrifuged,blow-dried and re-dissolved after 3 h of co-incubation in a water bath at 37℃.The samples were detected by ultra-high performance liquid chromatography Q Exactive mass spectrometry in ESI+mode,and the parent drug and its metabolites were examined by applying Full scan-ddMS^(2) data-dependent acquisition mode.Results After in vitro incubation with human liver microsomes,2C-B-FLY was metabolised to produce a total of four phase I metabolites and one acetylated phase II metabolite,which underwent metabolic reactions such as hydroxylation,debromination,and N-acetylation.25B-NBOH was metabolised to produce a total of eight phase I metabolites and two glucuronidated phase II metabolites,which comprised the major biotransformation reactions of O-demethylation,hydroxylation,amine dehydrogenation,N-dealkylation and glucuronidation.Conclusion This study describes the metabolites and metabolic pathways of 2C-B-FLY and 25B-NBOH in a human liver microsomal incubation system,providing a scientific basis for the in vivo detection of new psychoactive substance of the phenethylamine group.