高效液相色谱-紫外法检测家兔血浆美托洛尔的浓度及药动学  

HPLC-UV method for the determination of metoprolol in rabbit plasma and its application in pharmacokinetic study

作　　者：李沙[1] 王兴立[1] 符少莲[1] 李琳琳[1] 王开裕[1] 宋燕[1] 李晓飞[1] 马志国[1] 赵文[2] 

机构地区：[1]暨南大学药学院药剂学教研室,广东广州510632 [2]暨南大学药学院实验技术中心,广东广州510632

出　　处：《中国医院药学杂志》2012年第10期741-744,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家科技重大专项--"重大新药创制"专项(编号:2009ZX09501-023);暨南大学科研培育与创新基金研究项目(编号:21609504)

摘　　要：目的:建立高效液相色谱-紫外(HPLC-UV)方法测定家兔血浆中美托洛尔浓度并进行酒石酸美托洛尔片剂家兔体内药动学研究。方法:以Phenomenex C18柱(250 mm×4.6 mm,5μm)为分析柱,甲醇-水相(60∶40)为流动相(其中水相由385mL水、1.6 mL三乙胺和0.5 mL磷酸组成),紫外检测波长为223 nm,以苯妥英钠为内标,建立HPLC-UV法检测家兔血浆内美托洛尔的浓度。采用DAS3.0.1药动学软件计算药动学参数。结果:美托洛尔的线性范围为0.078～7.81μg·mL-1,最低定量限为0.078μg·mL-1,日内和日间精密度均小于10%,低、中、高3个质控浓度的提取回收率为87.5%～92.3%,准确度的范围在95.4%～108.6%。家兔口服酒石酸美托洛尔片后的主要药动学参数AUC0-t、tmax和Cmax分别为(338.8±30.9)mg.L-1.min、(45.0±0.0)min、(2.2±0.3)μg·mL-1。结论:该方法准确、快速、方便,为美托洛尔的药动学研究提供了简单易行的分析方法。OBJECTIVE A high performance liquid chromatography uhraviolet （HPLC-UV） method was developed and validated for determining the concentration of metoprolol in rabbit plasma. The pharmacokinetic study in rabbits was investigated. METHODS The HPLC-UV method was developed by using Phenomenex C18 column （250 ×4.6mm,5μm） for separation with phenytoin sodium as internal standard. The mobile phase was methanol-water （60：40） ,and the water phase consisted of 385 mL water, 1.6 mL triethylamine and 0. 5 mL phosphoric acid. The UV detection wavelength was 223 nm. DAS 3. 0. 1 pharmacokinetics software was used to calculate the pharmacokinetic parameters. RESULTS The linear range of metoprolol was 0. 078 - 7. 81 μg·mL-1, the limit of quantification was 0. 078μg·mL-1. Both the intra- and inter-day precisions were less than 10%. At low, medium and high quality control concentrations, the extraction recovery was in the range of 87.5% - 92. 3% and the accuracy ranged in 95.4% - 108.6% respectively. The method was applied for the pharmacokinetics study of metoprolol tartrate tablets by oral administration. The AUGht, tmax and Cmax were respectively （338.8 ± 30. 9） mg·L -1· min-1, （45.0 ± 0. 0） min and （2. 2 ± 0. 3）μg·mL-1 respectively. CONCLUSION The HPLC-UV method developed in this work is accurate, rapid and convenient. It provided a simple and easily available analytical method for the pharmacokinetics study of metoprolol.

关 键 词：美托洛尔 高效液相色谱-紫外法 药动学 

分 类 号：R969[医药卫生—药理学]