反相高效液相串联质谱检测方法快速测定人血浆中洛沙平的浓度及临床应用  

Rapid Determination of Loxapine in Plasma and Clinical Application by LC-ESI-MS/MS

作　　者：温预关[1] 廖日房[2] 曾转萍[3] 张明[1] 

机构地区：[1]广州市脑科医院国家药品临床研究基地,广东广州510370 [2]中山大学第二附属医院药剂科,广东广州510120 [3]广东药学院流行病学教研室,广东广州510224

出　　处：《今日药学》2008年第2期45-47,共3页Pharmacy Today

基　　金：广东省医院药学研究基金资助项目(编号:200714;2008B001);广州市医药卫生科技立项资助项目(编号:2007-YB-106)

摘　　要：目的建立测定人血浆中洛沙平浓度的反相高效液相串联质谱电喷雾检测方法(LC-ESI-MS/MS)。方法以迪马C18反相柱(DiamonsilTM C18 column,4.6mm×150mm,5μm)为色谱柱,流动相为甲醇-5mmol/L甲酸铵(90∶10),流速为1ml/min,柱温:25℃,以酸乙酯-二氯甲烷(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(SRM)对洛沙平(m/z328.1→271.2)和内标拉莫三嗪(m/z256→145)进行测定。并用此法测定24例患者稳态血药浓度。结果洛沙平的高(100μg/L)、中(50μg/L)、低(1μg/L)3个浓度的平均回收率分别为99.58%、96.45%和96.78%,日内(n=5)、日间(n=3)RSD均小于10%。线性范围为:0.5～250μg/L,回归方程为F=20.0874ρ+0.0166,r=0.999(n=9)。结论该方法灵敏、准确、简单、快速,可用于临床血浓监测和药动学研究。Obiective To set up a LC-ESI-MS/MS method for loxapine assay in plasma. Methods Loxapine was extracted with ethyl acetate-dichiloromethane （4 ： 1）. The residues were analyzed with a LC-ESI-MS/MS system （Dikma diamonsilTM C18 column, 4.6 mm × 150 mm, 5 μm）, with the mobile phase consisted of methanol：water with 5 mmol/L ammonium formate （90 ： 10）. A agilent 6410 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 328. 1 → 271.2 and m/z 256 → 145 was performed to detect loxapine and the internal standard, respectively. The method was used to evaluate the clinical application for 24 patients after multiple oral doses loxapine succinate tablets. Results The average recoveries for loxapine were 97.53%, 97.58%, and 102.22%, respectively. The within-day （n=5） and between--day （n=3） precision of variation was less than 10%. The calibration curves for loxapine had good linearity in the range of 0.5 - 250 μL, r=0.999 （n=9）. The limits of quantitation for loxapine was 0.5 μg/L（S/N〉20）. Conclusion The method provides a sensitive, accurate, precise, and reliable analytical procedure for clinical monitoring of loxapine plasma and its phamacokinetic studies.

关 键 词：洛沙平 血药浓度 反相高效液相串联质谱电喷雾法 

分 类 号：R969[医药卫生—药理学]