UPLC-Q-TOF-MS法鉴定连翘脂素在人肝微粒体中的代谢产物  

Metabolism Study of Phillygenin in Human Liver Microsomes by UPLC-Q-TOF-MS

作　　者：张晓旭[1] 贾佩佩[1] 张智勇[1] 张兰桐[1] ZHANG Xiao-xu JIA Pei-pei ZHANG Zhi-yong ZHANG Lan-tong(Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China)

机构地区：[1]河北医科大学药学院药物分析教研室,石家庄050017

出　　处：《中国药学杂志》2017年第3期226-230,共5页Chinese Pharmaceutical Journal

基　　金：河北省自然基金-石药集团医药联合研究基金资助项目(H2012206079)

摘　　要：目的建立体外人源肝微粒体孵育体系,应用UPLC-Q-TOF-MS法,首次对连翘脂素在人肝微粒体中的代谢产物进行鉴定。方法采用Phenomenex Kinetex C_(18)色谱柱(2.1 mm×100 mm,2.6μm),以0.1%甲酸水-乙腈为流动相进行梯度洗脱,流速为400μL·min^(-1);进样量5μL。采用正离子模式进行检测,电喷雾离子源,源温度为550℃,质量数扫描范围m/z 100~1 000。结果对ESI-MS正离子模式下连翘脂素可能的裂解途径进行了推测,同时鉴定了连翘脂素在肝微粒体中的8个代谢产物。结论所建立的连翘脂素在人肝微粒体中的UPLC-Q-TOF-MS测定法方便快捷,可应用于连翘脂素在人肝微粒中的代谢研究,同时为连翘脂素的药物代谢动力学提供了依据。OBJECTIVE To establish a UPLC-Q-TOF-MS method to characterize the metabolites of phillygenin in human liver mi- crosomal incubation system for the first time. METHODS The chromatography separation was performed on a Cls reversed phase LC column （Phenomenex Kinetex C18, 2. 1 mm × 100 mm, 2. 6 μm）. The mobile phase consisted of water-formic acid （ 100： 0. 1, V/V） mid acetonitrile and a gradient elution program was adopted at the flow rate of 400 μL · min-1. The mass spectral analysis was performed in a positive electrospray ionization mode, and the turbo spray temperature was 550 ℃. The full MS experiment was run with a scan range from m/z 100 to m/z l 000. RESULTS The possible fragmentation pathways of phillygein were speculated in a positive electrospray ion- ization mode, and eight metabolites was identified in human liver microsomal incubation systeM. CONCLUSION The UPLC-Q-TOF- MS method is very convenient and efficient for detecting phillygein in human liver mirosomes. The developed method is suitable for the metabolism research of phillygein in human liver microsomes, which providing valuable reference for pharmacokinetic study of phillygenin.

关 键 词：连翘脂素 人肝微粒体 体外代谢 超高效液相色谱串联四级杆飞行时间质谱 

分 类 号：R917[医药卫生—药物分析学]