液相色谱-串联质谱法快速测定人血浆中利培酮浓度.docVIP

液相色谱-串联质谱法快速测定人血浆中利培酮浓度 　 作者：温预关，廖日房，曾转萍，张明; 【摘要】; 目的 建立测定人血浆中利培酮浓度的反相高效液相串联质谱电喷雾检测法。方法 以迪马C18反相柱（ 4.6 mm×150 mm，5 μm）为色谱柱，流动相为甲醇5 mmol·L-1甲酸铵（体积比90∶10），流速为1 mL·min-1，柱温：25 ℃，以醋酸乙酯二氯甲烷（体积比4∶1）为提取剂。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，采用选择反应监测对利培酮（m/z 411→191）和内标拉莫三嗪（m/z 256→145）进行测定。结果 利培酮的高（50 μg·L-1）、中（25 μg·L-1）、低（1 μg·L-1）3个浓度的方法回收率均大于96%，提取回收率均大于85%，日内（n=5）、日间（n=3）RSD均小于10%；最低检测浓度为0.5 μg·L-1；线性范围为：0.5～100 μg·L-1,回归方程为F=55.9562ρ-0.3423，r=0.999（n=8）。结论 该方法灵敏、准确、简单、快速，可用于临床血药浓度监测和药动学研究。 【关键词】; 利培酮；血药浓度；拉莫三嗪；反相高效液相串联质谱电喷雾法 　　Abstract:Objective To set up a rapid analysis method of risperidone in plasma by liquid chromatographyelectrospray ionizationtandem mass spectrometry (LCESIMS/MS).Methods Risperidone was extracted from plasma with ethyl acetatedichiloromethane (4∶1).The residues were analyzed on a Dikma diamonsil C18 column (4.6 mm×150 mm，5 μm) with the mobile phase consisted of methanol and 5 mmol·L-1 of ammonium formate (90∶10).The flow rate was 1 mL·min-1 and column temperature 25 ℃.An Agilent 6410 triple quad mass spectrometer system equipped with an electrospray ionization iontrap source was used as the detector.The system was operated in the selected reaction monitoring mode transmitting m/z 411→191 transitions for both the analyte and the lamotrigine internal standard.Results The average recovery and extraction recovery for risperidone were more than 99.6% and 85%，respectively.The values for withinday and betweenday precision and accuracy were less than 10%.The calibration curves were linear over a concentration range of 0.5-100 μg·L-1(r = 0.998,n=8）.The limits of detection for risperidone was 0.5 μg·L-1 . Conclusion The method provides a sensitive,accurate,precise and reliable analytical procedure for clinical monitoring of plasma risperidone. 　　Keywords:risperidone；plasma concentration；lamotrigine;LCESIMS/MS 　　利培酮(risperidone)是一种选择性的单胺能拮抗剂，对5HT2受体、D2受体、α1及α2受体和H1受体亲和力高，临床上广泛用于治疗精神分裂症。其检测方法文献报道采用高效液相色谱法［1-3］和LCMS检测法［4-6］。为便于进行血药浓度监测和药动学研究，本文参照文献［