LC-ESI-MS/MS法快速测定人血浆中托莫西汀的浓度  

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

作　　者：陈楚雄[1] 李国成[1] 温预关[2] 吴翠芬[2] 

机构地区：[1]中山大学孙逸仙纪念医院药学部,广州510120 [2]广州市脑科医院国家药品临床研究基地,广州510370

出　　处：《中国临床药学杂志》2010年第6期365-368,共4页Chinese Journal of Clinical Pharmacy

基　　金：广东省自然科学研究基金资助(编号8151037001000001);广东省医学科研基金立项(编号A2008559);广东省医院药学研究基金资助(编号2010A08)

摘　　要：目的建立一种快速灵敏测定人体血浆中托莫西汀浓度的高效液相色谱串联质谱(LC-ESI-MS/MS)检测方法。方法以Agilent C_(18)反相柱(150 mm×2.1 mm,5μm)为色谱柱,流动相为乙腈(1%甲酸):0.02 mol·L^(-1)甲酸铵水溶液=80∶20(V/V);流速0.3 mL·min^(-1),柱温40℃。采用选择反应监测(SRM)对托莫西汀(m/z 256.1→44.1)和内标氟西汀(m/z 310.1→44.2)进行测定。结果托莫西汀的高(1 000μg·L^(-1))、中(500μg·L^(-1))、低(2μg·L^(-1))质量浓度标准血样的平均回收率分别为107.00%、103.51%和105.76%,日内(n=5)、日间(n=3)RSD均<15%;线性范围为1～1 500μg·L^(-1),回归方程为y=0.582 1ρ-2.581 4×10^(-4),r=0.997 5(n=5),分析方法的最低定量限为1μg·L^(-1)。结论该方法灵敏、准确、简单、快速,可用于托莫西汀临床血药浓度监测和药动学研究。AIM To establish a rapid and sensitive LC-ESI-MS/MS method for atomoxetine assay in plasma. METHODS Atomoxetine was extracted with ethyl acetate-dichloromethane. The residues were analyzed with a LC-ESI- MS/MS system （Agilent Eclipse Plus Cls column, 150 mm × 2.1 mm,5μm） with the mobile phase consisted of acetonitrile（ 1% formic acid） with 0.02 mol·L- 1 ammonium formate = 80： 20（ V/ V）, with a flow rate of 0.3 mL·min- 1 and temperature of 40℃. Selected reaction monitoring （SRM） using the precursor to product ion combinations of m/z 256.1→44.1 and m/z 310.1→44.2 was performed to detect atomoxetine and the internal standard, respectively. RESULTS The average recoveries for atomoxetine were 107.00%, 103.51% and 105.76%, respectively. The within-day （ n = 5） and between-day （ n = 3） precision of variation was less than 15%. The calibration curves for atomoxetine had good linearity within the range of 1 - 1 500μg- L- 1, r = 0. 997 5（ n = 5）. The limits of quantitation for palonosetmn was 1 μg·L-1. CONCLUSION The method provides a sensitive, accurate, precise and reliable analytical procedure for clinical monitoring of atomoxetine plasma and its phamaeokinefic studies.

关 键 词：托莫西汀 血药浓度 高效液相色谱串联质谱检测法 

分 类 号：R96[医药卫生—药理学]