液-质联用法同时测定人血浆伊潘立酮及其两个代谢产物浓度

Simultaneous determination of iloperidone and its two active metabolites in human plasma by LC-MS/MS

目的：建立LC．MS／MS法同时测定血浆伊潘立酮（iloperidone，ILP）及其两个代谢产物羟基伊潘立酮（hydroxyiloperidone，P88）和伊潘立酮羧酸（iloperidonecarboxylicacid，P95）的药浓度。方法：色谱柱为AgilentC。（100mm×4．6mm，3．5μm），流动相为乙腈-2mmol·L^-1醋酸铵水溶液（含1．5％甲酸）=28：72，流速为600μL·min-1，采用ESI源正离子模式，多反应监测方式测定。ILP，P88，P95的监测离子对分别为：m／z427．2-233．2，m／z429．2—261．2，m／z 429．2—233．2，内标氘代伊潘立酮（iloperidone—D3，ILP—D3）的监测离子对为m／z430．2—233．1。结果：血浆ILP，P88和P95浓度分别在0．0115ng·mL^-1，0．0115ng·mL^-1和0．0220ng·mL^-1范围内线性均良好，日间、日内精密度均在可接受范围内，提取回收率较高，均大于75％。结论：该方法准确、灵敏度高、重现性好，能够较好地应用于ILP及其两个代谢产物的人体药动学研究。

Objective： To establish an LC-MS/MS method for the determination of iioperidone （ILP） and its two active metabolites （P88 and P95） in human plasma. Methods： The separation was performed on the Agilent Cs column （100 mm x 4, 6 mm, 3.5 μm） , and the mobile phase was acetonitrile-2 mmol-L-1ammonium formate containing 1.5 % formic acid （28 ： 72） at a flow rate of 600 μL-1rain - 1. Electrospray ionization （ESI） source was applied and operated in multiple reaction monitoring （MRM） mode using the transitions of m/z 427. 2-1 233.2, 429.2-261.2, 429.2-233.2, and 430.2-233. 1 for ILP, P88, P95, and ILP-D3, respectively. Results： The method was validated over the concentration range of 0.01 - 15 ng· mL -1 for ILP and P88, and 0.02 20 ng-mL^-1 for P95, respectively. The intra- and inter-day precisions were within the acceptable range, and the mean extraction recoveries were more than 75%. Conclusion： The method is sensitive, accurate, and reproducible. It is applicable for the pharmaeokinetic study of ILP and its two active metabolites.