白屈菜碱在人肝微粒体中代谢产物的鉴定  

Identification of metabolites of chelidonine in human liver microsomes

作　　者：张瑜瑜 董文慧 徐静静[1] 朱辉[1] 李乐道[1] 孙璐[1] ZHANG Yuyu;DONG Wenhui;XU Jingjing;ZHU Hui;LI Ledao;SUN Lu(School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2018年第6期477-483,共7页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省大学生创新创业训练计划项目;沈阳药科大学中青年教师中长期培养计划项目(ZQN2015007)

摘　　要：目的研究白屈菜碱在人肝微粒体中的代谢情况。方法白屈菜碱与人肝微粒体进行体外共孵育,采用UPLC-MS技术,鉴定并推测了白屈菜碱在人肝微粒体中的代谢产物。色谱柱为Agilent Extend-C_(18)(150 mm×4.6 mm,5μm)柱,流动相采用体积分数0.1%甲酸水溶液(含浓度5 mmol·L^(-1)醋酸铵)-体积分数0.1%甲酸的甲醇(体积比为70∶30),流速为0.5 mL·min^(-1),采用ESI离子源,以正离子模式检测。结果通过色谱保留时间和质谱碎片等信息,在人肝微粒体中鉴定了原型化合物白屈菜碱,以及经氧化和脱亚甲基化反应得到的3个代谢产物。结论建立了白屈菜碱肝微粒体孵化模型和采用UPLC-MS技术鉴定白屈菜碱在人肝微粒体中的代谢产物的方法,初步推测含有羟基的代谢产物可能是白屈菜引起肝脏毒性的原因。Objective To study the metabolism of chelidonine in human liver microsomes. Methods chelidonine were incubated with human liver microsomes,and an ultra performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry（ UPLC/Q-TOF MS） method was developed to identify the metabolites of chelidonine in human liver microsomes. The chromatographic separation was performed on an Agilent Extend-C18（ 150 mm × 4. 6 mm,5 μm） using a gradient elution with mobile phase consisting of methanol containing 0. 1% formic acid and 5 m MNH4 AC containing 0. 1% formic acid（ 30∶70） and at 0. 5 m L·min-1 flowrate. A Micromass-Q-Tof Premier mass spectrometer coupled to an electrospray ionization（ ESI） source was operated in positive ion mode. Results A total of 3 metabolites,as well as parent compound,were identified in human liver microsomes by comparing the retention time and characteristic molecular and fragment ions. Two metabolites was formed by demethylene group from chelidonine. And one metabolite was oxidative metabolites of chelidonine. Conclusion The liver microsomal incubation model of chelidonine was established. An UPLC/Q-TOF MS method was developed to characterize the metabolites of chelidonine in human liver microsomes,which provided possible reasons for the study of hepatotoxicity by chelidonium majus.

关 键 词：白屈菜 白屈菜碱 人肝微粒体 代谢产物鉴定 肝脏毒性 超高效液相色谱串联四极杆飞行时间质谱 

分 类 号：R28[医药卫生—中药学] R917[医药卫生—中医学]