LC-MS法测定人血浆中格拉司琼的浓度

LC-MS determination of granisetron in human plasma

目的:建立高效液相色谱-电喷雾离子化质谱联用测定人血浆中格拉司琼浓度的方法,用于盐酸格拉司琼口腔崩解片的人体药代动力学和生物等效性研究。方法:使用Hypurity C18柱(210 mm×150 mm,5μm),以10 mmol·L-1甲酸铵-0.1%甲酸-乙腈(20∶30∶50)为流动相,流速为0.2 mL·min-1,柱温为40℃,以二级质谱选择离子反应监测(SRM)方式扫描检测。结果:格拉司琼的线性浓度范围为0.1～59.8 ng·mL-1(r=0.9973),最小检出浓度为0.06 ng·mL-1。提取回收率大于70%,平均相对回收率在80%～120%范围内。日内与日间RSD均小于15%。结论:本法简便、灵敏,可用于格拉司琼的药物代谢动力学和生物等效性研究。

Objective：To establish a method of HPLC - electrospray ion trap mass spectrometry to detect granise-tron in human plasma. Methods： Chromatographic column was Hypurity C 18 （ 210 mm × 150 mm, 5 μm ） ; The mobile phase was 10 mmol· L^- 1 ammonium formate - 0. 1% methanoic acid - acetonitrile （20： 30： 50） ; The flow rate was 0. 2 mL · min^-1 and temperature of column was 40℃. A MS/MS selective reaction monitoring mode was taken to quantitate granisetron in human plasma. Results：Standard curve was linear in the range of 0. 1 -59. 8 ng· mL^-1 （ r = 0. 9973 ）. The lower limit of detection of granisetron was 0. 06 ng·mL^-1. The absolute recovery was more than 70% and the relative recoveries of granisetron were in the range of 80% - 120%. Relative standard deviation of in-traday and interday assays of granisetron were both less than 15%. Conclusion ：The method is convenient and sensitive for detecting the concentration of granisetron in plasma, it can be used to study the pharmacokinetics and bio- equivalence of granisetron.