Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes
10.11665/j.issn.1000-5048.20220508
- VernacularTitle: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
- Author:
Shengfeng LIU
1
;
Lan ZHANG
;
Shucheng LIU
;
Chenzhi HOU
;
Peng XU
;
Bin DI
Author Information
1. 中国药科大学药物分析系
- Publication Type:Journal Article
- Keywords:
amide synthetic cannabinoids;
human liver microsomes;
phase I metabolism;
metabolic profile;
ADB-4en-PINACA;
4CN-CUMYL-BUTINACA;
5F-EMB-PICA;
4F-MDMB-BUTICA
- From:
Journal of China Pharmaceutical University
2022;53(5):577-590
- CountryChina
- Language:Chinese
-
Abstract:
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 phase I metabolites and their possible metabolic pathways.The results showed that there were 27 phase I metabolic pathways for the four amide synthetic cannabinoids, including hydroxylation, carboxylation, N-dealkylation and ester hydrolysis, with the main phase I metabolic 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.
