Metabolism of the synthetic cannabinoid PX-2 in human liver microsomes
10.16438/j.0513-4870.2019-0872
- VernacularTitle:合成大麻素PX-2在体外人肝微粒体中的代谢研究
- Author:
Hai HEI
1
;
Ying ZHANG
2
;
Duo-qi XU
3
;
Yan-yan WANG
2
;
Shi-yang QIN
2
;
Ji-fen WANG
1
;
Wen-fang ZHANG
2
Author Information
1. College of Criminal Science and Technology, People's Public Security University of China, Beijing 100038, China
2. The Judicial Identification Center of Beijing Public Security, Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing 100192, China
3. China University of Political Science and Law, Beijing 100091, China
- Publication Type:Research Article
- Keywords:
italic>N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide;
synthetic cannabinoids;
human liver microsomes;
metabolic pathway
- From:
Acta Pharmaceutica Sinica
2020;55(6):1201-1208
- CountryChina
- Language:Chinese
-
Abstract:
This study was performed to determine the metabolic profile of a new illicit drug, PX-2, in human liver microsomes. Q Exactive™ HF Quadrupole-Orbitrap LC-MS (LC-QE-HF-Orbitrap-MS) was employed to determine the metabolic sites and pathways of phase Ⅰ and phase II metabolism. PX-2 was added to a microsomal incubation model to simulate human hepatic metabolism. The results showed that a total of 18 phase Ⅰ metabolites and 3 glucuronidated phase II metabolites were generated, with the main metabolic pathways of phase Ⅰ metabolism including amide hydrolysis, fluoropentyl oxidative defluorination, benzyl hydroxylation, and carbazole ring hydroxylation. Based on the type and sites of metabolism, phase Ⅰ metabolites M1.1 (amide hydrolysis), M4.1 (carbazole cyclic hydroxylation), and M3.1 (oxidative defluorinative hydroxylation) are proposed to be potential poisoning markers. The results of this study provide a basis for identification of related drugs and establishment of testing methods in biological samples.
