化学
轨道轨道
微粒体
大麻素
兴奋剂
大麻素受体
羧酸酯酶
药理学
药物代谢
代谢途径
代谢物
酶
生物化学
受体
色谱法
质谱法
医学
作者
Hou Xiaoli,Ying Zhang,Duoqi Xu,Shiyang Qin,Chenyu Xue,Jifen Wang,Xinyang Zhou,Junjie Shangguan,Zhuoyan Li,Jiatong Liu,Zhenjun Jia,Jianghai Lu
标识
DOI:10.1016/j.jpba.2024.116342
摘要
A novel synthetic cannabinoid receptor agonist (SCRA), ADMB-FUBIATA, featuring an acetamide-linked structure, has emerged on the illicit drug market. To provide dependable verification of its consumption and identify reliable biomarkers, we investigated an in vitro metabolism study of ADMB-FUBIATA incubated with human primary hepatocytes (HPHs) for the first time and correlated our findings with those from human liver microsomes (HLMs). In this work, ADMB-FUBIATA (10 μM) was incubated with HLM and HPH for 1 and 5 h, respectively, and then subjected to LC-quadrupole-orbitrap MS. A total of 25 metabolites across 8 metabolic pathways were identified after incubation with HLM and HPH, respectively. Monohydroxylation and N-dealkylation were the major metabolic pathways, and formation to ketone was first identified. In addition, the metabolism of ADMB-FUBIATA were found to be mediated by multiple CYP450 enzymes, predominantly CYP2C19, 2D6, and 3A4. This research also initially characterized the fragmentation patterns of the metabolites of ADMB-FUBIATA, elaborating on their structural relationship with ADMB-FUBIATA analogs. To effectively monitor ADMB-FUBIATA abuse, metabolites M4 and M1 were proposed as reliable biomarkers by cross-validating the HLM and HPH incubation results.
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