枸橼酸爱地那非人肝微粒体代谢产物鉴定及性别差异  

Metabolites Identity and Gender Differences of Aildenafil Citrate in Human Liver Microsomes

作　　者：赵晓悦 宋俊科[1] 杜冠华[1] ZHAO Xiaoyue;SONG Junke;DU Guanhua(Beijing Key Lab of Drug Target and Screening Research,Institute of Materia Medica, Peking Union Medical College&Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]北京协和医学院&中国医学科学院药物研究所药物靶点研究与新药筛选北京市重点实验室,北京100050

出　　处：《医药导报》2020年第11期1491-1495,共5页Herald of Medicine

基　　金：国家重点研发计划(2016YFC1000905)。

摘　　要：目的研究枸橼酸爱地那非在不同性别来源的人肝微粒体体外代谢孵育体系中的代谢差异。方法将枸橼酸爱地那非与不同性别来源的人肝微粒体进行体外共孵育,采用超高效液相色谱-四极杆-飞行时间质谱仪,鉴定并推测爱地那非在不同性别来源的人肝微粒体中的代谢产物。色谱柱为Acquity UPLC BEH C18(2.1 mm×100 mm×1.7μm),流动相为乙腈与0.4%甲酸溶液,梯度洗脱,流速0.3 mL·min-1。采用电喷雾离子源,正离子模式检测。结果结合色谱保留时间和质谱碎片离子信息,在体外肝微粒体孵育体系中鉴定了原型分子爱地那非,以及爱地那非经Ⅰ相代谢反应产生的8种代谢产物。所有代谢产物均为水溶性分子,无明显毒性结构。不同性别肝微粒体孵育体系中检测到的代谢产物种类相同。结论建立了爱地那非的体外肝微粒体孵育体系模型,初步研究推测不同性别人群对爱地那非的肝脏微粒体代谢过程一致。Objective To investigate the differences in aildenafil citrate metabolites in liver microsomes from different genders.Methods Aildenafil citrate were incubated with human liver microsomes from different gender in vitro,and a UPLC/Q-TOF MS method was developed to identify the metabolites of aildenafil in human liver microsomes from different genders.The chromatographic separation was performed on an Acquity UPLC BEH C18(2.1 mm×100 mm×1.7μm)using a gradient elution with the mobile phase consisting of acetonitrile and methanol containing 0.4%formic acid at 0.3 mL·min-1 flow rate.A Micro mass-Q-Tof Premier mass spectrometer coupled to an ESI source was operated in positive ion mode.Results By comparing the retention time and fragment ions,8 kinds of metabolites,as well as the parent compound,were identified in human liver microsomes from different genders.All metabolites were water-soluble molecules without obvious toxic structure.There were no differences among metabolites of different groups.Conclusion The liver microsomal incubation model of aildenafil citrate was established,and the research provided possible reasons that aildenafil citrate had consistent liver metabolic processes in different gender groups.

关 键 词：爱地那非 枸橼酸 肝微粒体 代谢产物 性别差异 

分 类 号：R917[医药卫生—药物分析学] R927.1[医药卫生—药学]