LC-ESI-MS/MS法快速测定人血浆中舍吲哚的浓度  

Rapid determination of sertindole in plasma by LC-ESI-MS/MS

作　　者：温预关[1] 戴婕[2] 李芳芳[1,3] 张明[1] 倪晓佳[1] 邱畅[1] 

机构地区：[1]广州市脑科医院国家药品临床研究基地,广州510370 [2]中山大学附属孙逸仙医院药剂科,广州510120 [3]广东药学院中药学院,广州510224

出　　处：《中国临床药学杂志》2013年第1期6-9,共4页Chinese Journal of Clinical Pharmacy

基　　金：国家自然科学基金(编号10926191);广东省重大科技计划(编号2011A080300003);广东省科技计划社会发展领域(编号00498500130062027);广东省药学会(编号2012A02)

摘　　要：目的建立测定人血浆中舍吲哚浓度的高效液相色谱串联质谱电喷雾法(LC-ESI-MS/MS)。方法固定相:Agilent Eplic plus Zobax-C_(18)(50mm×4.6 mm,3.5μm);流动相:甲醇-0.005 mol·L^(-1)甲酸铵水溶液(90:10,含0.1%甲酸);流速0.5 mL·min^(-1);柱温40℃。以V(醋酸乙酯):V(二氯甲烷)=4:1为提取液。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择性离子监测(SRM)对舍吲哚(m/z 441.3→113.2)和内标奥氮平(m/z 313.0→256.0),同时对18例患者多次口服舍吲哚片后稳态血药浓度进行监测。结果在质量浓度1~500μg·L^(-1)内线性关系良好(r=0.999 4,n=7),低(2.5μg·L^(-1))、中(100μg·L^(-1))、高(300μg·L^(-1))3个质量浓度舍吲哚的方法回收率分别为97.79%、98.75%和100.94%,日内和日间精密度良好(RSD均<15%)。结论该方法灵敏、准确、简单、快速,可用于舍吲哚临床血药浓度监测和药动学研究。AIM To set up a LC-ESI-MS/MS method for sertindole assay in human plasma. METHODS Sertin- dole was extracted with ethyl acetate： dichloromethane（ V： V = 4：1）. The residues were analyzed with a LC-ESI-MS/MS system （Agilent Eplic plus Zobax-C18 column, 50 mm× 4.6 mm, 3.5 μm） with the mobile phase consisted of methanol： water with 5 mmol· L-1 armnonium formate （90： 10,with 0.1% formic acid） .The flow rate was 0.5 mL＇min-1 ,and the column temperature was 40℃. An Agilent triple quad mass spectrometer system equipped with an electrospray ionization ion-trap source was used as the detector and operated in the positive ion mode. Selected reaction monitoring（SRM） using the precursor to product ion combinations of m/z 441.3→113.2 and m/z 313.0→256.0 was performed to detect serfindole and the intemal standard, respectively. The method was used to evaluate clinical application for 18 patients after multiple oral doses of sertindole tablets. RESULTS The average method recoveries for three sertindole concentrations （2.5,100 and 300μg·L-1） were 97.79%, 98.75% and 100.94% ,respectively. The within-day （ n = 5） and be- tween-day （n = 3） precision of variation was less than 15%. The calibration curves for sertindole had good linearity, r = 0.999 4（ n = 7）, over the range of 1 - 500μg·L-1. The limits of quantitation for sertindole were 1μg·L-1. CON- CLUSION The method provides a sensitive, accurate, precise and reliable analytical procedure for clinical monitoring of sertindole plasma concentration and phamacokinetic studies.

关 键 词：舍吲哚 血药浓度 高效液相色谱串联质谱电喷雾法 

分 类 号：R96[医药卫生—药理学]