HPLC-MS/MS法快速测定人血浆中美利曲辛及生物等效性研究  

Rapid determination of melitracen in plasma by HPLC-MS/MS and its bioequivalence

作　　者：谭献文[1] 廖日房[2] 温预关[3] 

机构地区：[1]广州市第一人民医院药剂科,广东广州510180 [2]中山大学附属第二医院药剂科,广东广州510120 [3]广州市脑科医院国家药品临床研究基地,广东广州510370

出　　处：《现代生物医学进展》2009年第12期2336-2338,2363,共4页Progress in Modern Biomedicine

基　　金：广东省自然科学研究基金资助(8151037001000001)

摘　　要：目的：建立测定人血浆中关利曲辛浓度的高效液相串联质谱法（HPLC—MS／MS），用于氟哌噻吨美利曲辛片的生物等效性研究。方法：以Agilent ZORBAX EclipsePlus C18（4．6mm×150mm，5um）为色谱柱，流动相为乙腈（含1％甲酸）：0．02mo·L-1甲酸铵水溶液（80：20，V：V），流速：0．8mL·min-1；柱温：40℃，以醋酸乙酯：二氯甲烷（4：1，V：V）为提取荆。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）对关利曲辛（m／z292．2→232．2）和阿米替林（m／z278．1→91．0）进行测定。结果：美利曲辛的高（50μg·L-1）、中（20μg·L-1）、低（0．5μg·L-1）3个浓度的平均回收率分别为97．53％、104．03％和106．87％，日内（n=5）、日间（n=3）RSD均小于15％；分析方法的最低定量限为0．2μg·L-1。线性范围为：0．2-60μg·L-1，回归方程为：F=1．8691p＋0．0555，r=0．9986（n=9），权重为1／p2。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。Objective： To develop a HPLC-MS/MS method for melitracen assay in plasma and its bioequivalence. Methods： Meli- tracen was extracted with ethyl acetate-dichloromethane. The residues were analyzed with a HPLC-MS/MS system （Agilent ZORBAX Eclipse Plus C18,4.6 mm×150 mm, 5 μm） with the mobile phase composed of acetonitrile （1% formic acid） with 0.02 mol.L-1 ammonium formate （80：20, v/v）. 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 292.2→232.2 and m/z 278.1→91.0 was performed to detect melitracen and the internal standard, respectively. Resultx The average recoveries for melitracen were 97.53 %, 104.03 % and 106.87 % respectively. The within-day （n=5） and between-day （n=3） precision was less than 15 %. The calibration curves for melitracen had good linearity over the range of 0.2-601μg·L-1 with r = 0.9986 （n=9）. The limits of quantitation for melitracen was 0.2 μg·L-1. Conclusions： This paper provides a sensitive, accurate, precise and reliable analytical procedure for clinical monitoring ofmelitracen plasma and its phamacokinetic studies.

关 键 词：美利曲辛 血药浓度 高效液相串联质谱法 

分 类 号：R927.1[医药卫生—药学]