去氢厄弗酚在小鼠肝微粒体中代谢产物及CYP450酶亚型的鉴定

目的建立去氢厄弗酚(DHE)小鼠体外肝微粒体孵育方法,鉴定DHE在小鼠肝微粒体中的代谢产物及参与DHE代谢的CYP450酶亚型。方法采用UPLC-Q-TOF-MS/MS分析鉴定DHE在体外肝微粒体共温孵后的代谢产物,筛选7种CYP450酶亚型,并通过特异性化学抑制剂法,鉴别参与DHE代谢的主要CYP450酶亚型。结果在体外肝微粒体共温孵后,检测到4个代谢产物;所筛选的7种CYP450酶亚型中,CYP1A2、CYP2C8和CYP2D2对DHE体外肝微粒体代谢的参与度较高。结论在肝脏中,有多种代谢酶亚型参与DHE的代谢,表明DHE在临床上不易与其他药物产生相互作用。

Identification of dehydroeffusol metabolites and related CYP450 metabolic isoforms in mice liver microsomes

Objective To establish a method for identification of the dehydroeffusol (DHE) metabolites in mice liver microsomes, and to identify the CYP450 isoforms involved in DHE metabolism.Methods The DHE metabolites in vitro incubated in liver microsomes were identified by UPLC-Q-TOF-MS/MS,and 7 types of CYP450 isoforms were screened out,the specific chemical inhibitors were used to identify the CYP450 isoforms involved in DHE metabolism.Results 4 metabolites were detected after in vitro incubation with mice liver microsomes.In the 7 CYP450 isoforms screened,CYP1A2,CYP2C8 and CYP2D2 were highly involved in the metabolism of DHE in liver microsomes.Conclusion In liver,there are a several subtypes of CYP450 enzymes involved in the metabolism of DHE metabolism,indicating that DHE is difficult to interact with other drugs in clinical.