摘要
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 HPLC-MS/MS method for determing 5-hydroxylansoprazole/ lansoprazole sulfone, and optimize the incubated conditions for rat liver microsomes. METHODS 5-Hydroxylansoprazole/ lansoprazole were determined by HPLC-MS/MS. Single factor design was used to optimize the incubated conditions and the enzymes kinetics value was evaluated by graphical analysis with Lineweaver-Burk double reciprocal plots. RESULTS The linear range of 5-hydroxy lansoprazole and lanso-prazole sulphone in liver microsome incubation system were 5.57 -2 520 and 5.42 -2 480 ng·mL^-1, respectively. The optimal incubated conditions were 10 μmol·L^-1 lansoprazole, 0. 16 mg liver microsomes, and 10min incubation, respectively. CONCLUSION The HPLC-MS/MS method is accurate and suitable for the determination of 5-hydroxy lansoprazole and lansoprazole sulfone in rat liver microsomes. The incubated condition can be applied for study in the drug interaction with lansoprazole.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2012年第1期49-53,共5页
Chinese Pharmaceutical Journal
