论文部分内容阅读
目的建立大鼠肝微粒体酶孵育系统中兰索拉唑代谢产物5-羟基兰索拉唑及兰索拉唑砜的检测方法,并对体外孵育条件进行优化。方法采用HPLC-MS/MS测定微粒体酶孵育系统中代谢产物的浓度,用单因素法对各孵育条件进行优化,采用Lineweaver-Burk双倒数法研究CYP2C19及CYP3A4的酶促动力学。结果 5-羟基兰索拉唑、兰索拉唑砜分别在5.57～2 520、5.42～2 480 ng.mL-1内线性关系良好。体外酶孵育条件为:兰索拉唑10μmol.L-1,肝微粒体酶量0.16 mg,孵育时间为10min。结论本实验建立的HPLC-MS/MS的方法快捷、灵敏,适用于兰索拉唑两种代谢产物的测定。体外酶孵育条件的优化,同时也为研究其他多种经CYP2C19及CYP3A4代谢的药物对兰索拉唑的代谢影响及相互作用奠定了基础。
OBJECTIVE To establish a method for the determination of lansoprazole metabolites 5-hydroxy-lansoprazole and lansoprazole sulfone in the rat liver microsomal enzyme incubation system and to optimize the in vitro incubation conditions. Methods The concentration of metabolites in microsomal enzyme incubation system was determined by HPLC-MS / MS. The conditions of incubation were optimized by single factor method. The enzymatic kinetics of CYP2C19 and CYP3A4 were studied by using Lineweaver-Burk double reciprocal method. Results The linear relationship between 5-hydroxy-lansoprazole and lansoprazole sulfone in 5.57 ~ 2 520,5.42 ~ 2 480 ng.mL-1 was good. In vitro enzyme incubation conditions: lansoprazole 10μmol.L-1, liver microsomal enzyme amount 0.16 mg, incubation time was 10min. Conclusion The HPLC-MS / MS method established in this experiment is fast and sensitive and suitable for the determination of two metabolites of lansoprazole. In vitro enzyme incubation conditions optimization, but also for the study of a variety of other CYP2C19 and CYP3A4 metabolism of lansoprazole metabolism and the basis of the interaction.