LC-MS法检测大鼠血浆中酒石酸美托洛尔的方法学研究  

Quantitative determination of metoprolol by liquid chromatography mass spectrometry in rat plasma

作　　者：张帆[1] 崔孟珣[1] 张振清[1] 

机构地区：[1]军事医学科学院毒物药物研究所,军事医学科学院药物代谢与药代动力学重点实验室,北京100850

出　　处：《军事医学科学院院刊》2009年第6期543-545,共3页Bulletin of the Academy of Military Medical Sciences

基　　金：“国家重大新药创制”科技重大专项综合性新药研究开发技术大平台(2009ZX09301-002);“国家重大新药创制”科技重大专项新药研究开发技术单元平台(2009ZX09304-004)

摘　　要：目的:建立准确、灵敏、可靠的LC-MS法检测大鼠血浆中酒石酸美托洛尔的浓度。方法:血浆样品用乙酸乙酯液-液萃取,内标选用盐酸普萘洛尔,液相色谱柱为ThermoODS-C18(5.0μm,100mm×2.1mm),流动相为含0.1%甲酸的乙腈:甲醇:水(20:20:60,体积比),流速为0.2ml/min;仪器选用Agilent公司1100LC/MSDSL型液相色谱-质谱联用仪,采用电喷雾离子化电离源(ESI),选择性离子监测(SIM)方式进行正离子检测,用于定量分析的离子反应分别为m/z267→268(美托洛尔)和m/z259→260(普萘洛尔)。结果:在本实验条件下,美托洛尔与内标盐酸普萘洛尔分离良好,保留时间分别为1.79和4.01min,0.1～50ng/ml范围内线性关系良好(r2=0.99411),提取回收率均大于80%,日内日间精密度均小于15%(n=5)。结论:该方法快速、准确、灵敏度高,专属性好,可用于酒石酸美托洛尔在大鼠体内药物代谢动力学的研究。Objective：To establish a highly sensitive,rapid and selective liquid chromatography mass spectrometry （LC-MS） method for the determination of metoprolol in rat plasma.Methods：A simplified liquid-liquid extraction with acetidin was employed for the sample preparation.The separation was carried out on a Thermo ODS-C18（5 μm,100 mm×2.1 mm）.The mobile phase consisted of acetonitrile-methanol-water（20∶20∶60）.Propranolol was used as the internal standard.The detection was performed on a liquid chromatography mass spectrometry by selected ion monitoring （SIM） scan mode electrospray ionization（ESI）. Results and Conclusion：The range of calibration curve was 0. 1 -50 ng/ml and the limit of quantification was 0.1 ng/ml. The intra- and inter-day precision RSD was less than 15%. This method is sensitive, simple, rapid and suitable for the pharmacokinetic study of metoprolol.

关 键 词：美托洛尔 药代动力学 液相质谱法 

分 类 号：R969.1[医药卫生—药理学]