4种酰胺类合成大麻素在人肝微粒体中Ⅰ相代谢规律研究  

PhaseⅠmetabolism of four amide synthetic cannabinoids in human liver microsomes

作　　者：刘生凤 张岚[1,2] 刘书丞 侯臣之 徐鹏 狄斌[1,2] LIU Shengfeng;ZHANG Lan;LIU Shucheng;HOU Chenzhi;XU Peng;DI Bin(Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009;China National Narcotics Control Commission-China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control,Nanjing 210009;Key Laboratory of Drug Monitoring and Control,Drug Intelligence and Forensic Center,Ministry of Public Security,Beijing 100193,China)

机构地区：[1]中国药科大学药物分析系,南京210009 [2]国家禁毒委员会办公室-中国药科大学禁毒关键技术联合实验室,南京210009 [3]公安部禁毒情报技术中心,毒品监测管控与禁毒关键技术公安部重点实验室,北京100193

出　　处：《中国药科大学学报》2022年第5期577-590,共14页Journal of China Pharmaceutical University

摘　　要：研究4种近来滥用的酰胺类合成大麻素ADB-4en-PINACA、4CN-CUMYL-BUTINACA、5F-EMB-PICA和4F-MDMBBUTICA的体外人肝微粒体代谢规律。取人肝微粒体,加合成大麻素使成1 mg/mL,模拟人体代谢过程孵育10 min、60 min或3 h,用液相色谱-四极杆-飞行时间串联质谱(LC-QTOF-MS)分析技术检测并鉴定代谢产物的结构,探索代谢途径。结果显示,5F-EMB-PICA、4F-MDMB-BUTICA、ADB-4en-PINACA和4CN-CUMYL-BUTINACA存在羟基化、羧基化、N-脱烷基和酯水解等27种Ⅰ相代谢途径,其中主要的Ⅰ相代谢途径为酯水解、双键氧化成邻二醇、氧化脱氟羧基化、单羟基化(烷基侧链或吲哚/吲唑环)和N-脱烷基。本研究可为司法鉴定4种酰胺类合成大麻素的滥用和污水毒情评估提供潜在的检测标志物。This study was performed to determine the metabolic profile of four amide synthetic cannabinoids that recently abused,i.e.,ADB-4en-PINACA,4CN-CUMYL-BUTINACA,5F-EMB-PICA and 4F-MDMB-BUTICA,in human liver microsomes(HLMs).The four amide synthetic cannabinoids were added to the microsomal incubation model,being incubated for 10 min,60 min or 3 h to simulate human hepatic metabolism.Liquid chromatography quadrupole time-of-flight mass spectrometry(LC-QTOF-MS)analytical instrument was employed to determine and speculate the structure of PhaseⅠmetabolites and their possible metabolic pathways.The results showed that there were 27 PhaseⅠmetabolic pathways for the four amide synthetic cannabinoids,including hydroxylation,carboxylation,N-dealkylation and ester hydrolysis,with the main PhaseⅠmetabolic pathways of ester hydrolysis,dihydrodiol(pentenyl tail),oxidative defluorination to carboxylic acid,monohydroxylation(alkyl side chain or indole/indazole ring)and N-dealkylation.The results of this study may provide potential detection markers for forensic identification and sewage abuse assessment of the four amide synthetic cannabinoids.

关 键 词：酰胺类合成大麻素 人肝微粒体 Ⅰ相代谢 代谢规律 ADB-4en-PINACA 4CN-CUMYL-BUTINACA 5F-EMB-PICA 4F-MDMB-BUTICA 

分 类 号：R917[医药卫生—药物分析学]