HPLC-MS-MS法测定人血浆中托吡酯的浓度  

Determination of topiramate in human plasma by liquid chromatography-tandem mass spectrometry

作　　者：赵娜[1] 刘雪松[2] 闫冬[1] 赵春艳[2] 于彬[1] 高静[1] 

机构地区：[1]沈阳亿灵医药科技有限公司,沈阳110179 [2]辽宁中医药大学附属第二医院,沈阳110034

出　　处：《中国新药杂志》2011年第12期1108-1111,共4页Chinese Journal of New Drugs

摘　　要：目的：建立测定人血浆中托吡酯浓度的HPLC-MS-MS方法。方法：采用液液萃取法,以甲基叔丁基醚为提取溶剂;HPLC采用Hypersil ODS C18色谱柱（150 mm×4.6 mm,5μm）,流动相为5 mmol·L-1醋酸铵溶液-甲醇（25∶75）,流速0.5 mL·min-1;质谱采用ESI源,负离子检测模式,定量分析离子为托吡酯m/z338.1[M-H]-→78.0,双氯芬酸钠m/z294.1[M-H]-→249.7。结果：人血浆中托吡酯的标准曲线范围为10.00~3 600.00 ng.mL-1（n=7）,r〉0.999;日内和日间精密度均小于8.9%;提取回收率（低、中、高）分别为（75.5±3.1）%,（77.0±1.6）%和（72.8±1.5）%,内标提取回收率为（76.1±3.5）%;基质效应（低、中、高）分别为（99.2±5.6）%,（98.9±4.2）%和（99.4±3.8）%,内标基质效应为（100.4±1.3）%。结论：该方法灵敏、快速、专属性强,可用于人血浆中托吡酯浓度的测定。Objective： To develop an HPLC-MS-MS method for determination of topiramate in human plasma.Methods： Plasma samples were extracted using methyl tertiary butyl ether,and separated on a Hypersil ODS C18 column（150 mm×4.6 mm,5 μm） with aqueous solution（5 mmol·L-1 ammonium acetate buffer）-methanol（25∶75） as mobile phase with a isocratic mode,and at a flow rate of 0.5 mL·min-1.ESI was used as the ion source,and diclofenac sodium as the internal standard.The target compounds topiramate and diclofenac sodium were quantified with m/z 338.1 -→ 78.0 and 294.1→ 249.7,respectively.Results： Calibration curve was obtained in the range of 10.00~3 600.00 ng·mL-1（n=7）,r0.999.The inter-and intra-day precisions（RSD） were within 8.9%.The extraction recoveries of topiramate at low,middle,high level were（75.5±3.1）%,（77.0±1.6）% and（72.8±1.5）%,respectively;the internal standard the extraction recovery was（76.1±3.5）%.Matrix effect of topiramate at low,middle,high level were（99.2±5.6）%,（98.9±4.2）% and（99.4±3.8）%,respectively;the internal standard the matrix effect was（100.4±1.3）%.Conclusion： The method is accurate,sensitive and simple for determination of topiramate in human plasma.

关 键 词：HPLC-MS-MS 托吡酯 双氯芬酸钠 液液萃取 

分 类 号：R971[医药卫生—药品]