HPLC-MS/MS测定大鼠肝微粒体孵育体系中兰索拉唑代谢产物浓度  

Determination of 5-Hydroxylansoprazole/Lansoprazole Sulfone by HPLC-MS/MS in Incubation System in Vitro

作　　者：张程亮[1] 向道春[1,2] 高萍[1] 任秀华[1] 刘东[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,武汉430030 [2]荆州市第一人民医院药学部,湖北荆州434000

出　　处：《中国药学杂志》2012年第1期49-53,共5页Chinese Pharmaceutical Journal

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.

关 键 词：细胞色素P450酶 高效液相色谱-质谱联用 兰索拉唑 5-羟基兰索拉唑 兰索拉唑砜 

分 类 号：R917.1[医药卫生—药物分析学]