电喷雾离子阱二级质谱法测定人血浆中利培酮浓度

Determination of risperidone in human plasma with LC-ESI-MS/MS

目的建立电喷雾离子阱二级质谱法(LC-ESI-MS/MS)测定人血浆中利培酮浓度。方法色谱柱DiamonsilTMC18(4.6 mm×150mm,5μm);流动相∶乙腈(1%甲酸)∶0.02 mol.L-1醋酸铵=(60∶40,V∶V),流速:0.8 mL.min-1;柱温:25℃;进样体积:10μL;质谱条件为电喷雾离子源,检测方式为正离子多离子反应监测(MRM),用于定量分析的离子为利培酮m/z411→191,内标替米沙坦m/z516→497,生物样本采用醋酸乙酯:二氯甲烷(4∶1)液液萃取处理。结果利培酮血药浓度线性范围为0.5～50μg.L-1,线性方程为C=2.38F-0.24,r=0.999(n=7),最低检测浓度为0.1μg.L-1,高中低三个浓度的提取回收率分别为71.70%,64.58%,64.93%,日内、日间RSD均小于15%。结论本法灵敏、准确、快速,可用于临床常规血药浓度测定和药动学研究。

OBJECTIVE To establish a LC-ESI-MS/MS method for the determination of risperidone in human plasma. METHODS HPLC ： Use DiamonsilTM C 18 （4.6 mm × 150mm ,5 μm）, the mobile phase consisting of acetonitrile （ 1% methanoic acid） - 0. 02 mol · L^- 1 annoniun acetate （60： 40, V/V）, the flow rate was 0. 8mL · min^ - 1, the Column temperature was 25℃. MS： Use gas-auxiliary electrospray ionization source. Risperidone （ MRM m/z 411→191 ） and telmisartan（ MRM m/z 516→497） were detected by the LC/MSD Trap XCT analyser. The plasma samples were done by a single step liquid-liquid extracted with the mixture of ethyl acetate and dichloromethane at .the ratio of 4： 1（V/V）. RESULTS The linear calibration curves were obtained in the range of 0. 5 -50μg · L^-1 for risperidone in human plasma（ r = 0. 999, n = 7 ）. The limits quantitation for risperidone was 0. 11μg · L^-1. The within-day and between-day precision of variation was less than 15%. The average recoveries for risperidone were 71.70% ,64. 58% and 64. 93%, respectively. CONCLUSION The analytical method appeared to be accurate, sensitive and convenient. It is suitable for the determination of risperidone in human plasma.