In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s
In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s
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DOI：
10.1016/j.jpba.2015.11.023
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发表时间：
2016-02-05
影响因子：
3.4
通讯作者：
Lee, Hye Suk
中科院分区：
文献类型：
--
作者：
Kim, Ju Hyun;Kim, Hee Seung;Lee, Hye Suk
采用液相色谱-高分辨质谱法（LC-HRMS）研究了一种新的合成大麻素EAM-2201在人肝微粒体和主要cDNA表达的细胞色素P450（CYP）同工酶中的体外代谢。在NADPH存在下，EAM-2201与人肝微粒体孵育导致形成37种代谢物，包括9种羟基-EAM-2201（M1-M9）、5种二羟基-EAM-2201（M10-M14）、二氢二醇-EAM-2201（M15）、氧化脱氟EAM-2201（M16）、2种羟基-M16（M17和M18）、三个二羟基-M16（M19-M21）、N-脱烷基-EAM-2201（M22）、两个羟基-M22（M23和M24），二羟基-M22（M25），EAM-2201 N-戊酸（M26），羟基-M26（M27），脱氢-EAM-2201（M28），羟基-M28（M29），七羟基-M28（M30-M36），和氧化脱氟羟基-M28（M37）。EAM-2201的代谢涉及多种CYP，包括CYP 1A 2、2B 6、2C 8、2C 9、2C 19、2D 6、2 J2、3A 4和3A 5。总之，EAM-2201被CYP广泛代谢，其代谢产物可用作EAM-2201滥用的指标。(C)2015爱思唯尔B. V.保留所有权利。
In vitro metabolism of a new synthetic cannabinoid, EAM-2201, has been investigated with human liver microsomes and major cDNA-expressed cytochrome P450 (CYP) isozymes using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Incubation of EAM-2201 with human liver microsomes in the presence of NADPH resulted in the formation of 37 metabolites, including nine hydroxy-EAM-2201 (M1-M9), five dihydroxy-EAM-2201 (M10-M14), dihydrodiol-EAM-2201 (M15), oxidative defluorinated EAM-2201 (M16), two hydroxy-M16 (M17 and M18), three dihydroxy-M16 (M19-M21), N-dealkyl-EAM-2201 (M22), two hydroxy-M22 (M23 and M24), dihydroxy-M22 (M25), EAM-2201 N-pentanoic acid (M26), hydroxy-M26 (M27), dehydro-EAM-2201 (M28), hydroxy-M28 (M29), seven dihydroxy-M28 (M30-M36), and oxidative defluorinated hydroxy-M28 (M37). Multiple CYPs, including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, and 3A5, were involved in the metabolism of EAM-2201. In conclusion, EAM-2201 is extensively metabolized by CYPs and its metabolites can be used as an indicator of EAM-2201 abuse. (C) 2015 Elsevier B.V. All rights reserved.