LC-MS/MS法测定人血浆中奈比洛尔浓度及其在中国人体内的药代动力学  

Determination of nebivolol in human plasma by LC-MS/MS and study of its pharmacokinetics on the Chinese

作　　者：司倩[1] 陈渊成[1] 黄黎华[1] 程昱[1] 何华[1] 柳晓泉[1] 

机构地区：[1]中国药科大学药物代谢与动力学研究中心,南京210009

出　　处：《中国药科大学学报》2011年第2期136-140,共5页Journal of China Pharmaceutical University

摘　　要：本文建立了一种快速测定人血浆中奈比洛尔血药浓度的LC-MS/MS法,并研究其在中国健康人体内的药代动力学行为。以氨氯地平作为内标,采用C18反相柱(150 mm×2.0 mm,4.6μm),柱温35℃。流动相为乙腈-水(含0.05%甲酸)(45∶55),流速0.2 mL/min;电喷雾离子化(ESI),正离子扫描,选择性反应监测(SRM)药和内标分别为:奈比洛尔m/z406.2→151.0;氨氯地平m/z 409.0→238.2。在本文建立的方法下,奈比洛尔在0.025～25 ng/mL呈良好的线性关系,r=0.998 6,最低检测浓度为0.008 ng/mL,低、中、高浓度下的回收率、日内及日间精密度均符合方法学要求。健康受试者口服5 mg奈比洛尔片后的t1/2,AUC0-t,cmax,MRT分别为:(14.4±5.5)h,(7.35±2.48)ng.h/mL,(1.05±0.35)ng/mL,(16.5±5.3)h。结果表明:该方法专属性强,适用于奈比洛尔血样的定量分析。A simple,sensitive and rapid liquid chromatographic-electro-spray ionization tandem mass spectrometric method was developed for the quantification of nebivolol in human plasma.Amlodipine was used as the internal standard（IS）.Separation was performed using a Shimadzu C18 column（150 mm×2.0 mm,4.6 μm） maintained at 35 ℃ and the mobile phase consisting of a mixture of acetonitrile and water（containing 0.05% formic acid）（45∶ 55） was delivered at a flow rate of 0.2 mL/min;The analytes were analyzed by electro-spray ionization（ESI） in the selected reaction monitoring mode.The precursor to product ion transitions of m/z 406.2-151.0 and m/z 409.0-238.2 were used to measure nebivolol and the IS,respectively.The linearity ranged from 0.025 to 25 ng/mL（r = 0.998 6）;and the limit of detection of nebivolol in human plasma was 0.008 ng/mL.The recovery,intra-and inter-assay precisions met the requirements of bioanalytical method.The t1/2,AUC0-t,cmax,MRT of nebivolol in healthy volunteers were（14.4±5.5） h,（7.35±2.48） ng ·h/mL,（1.05±0.35） ng/mL,and（16.5±5.3） h for a single oral dose of 5 mg nebivolol,respectively.The method is selective and suitable for the quantification of nebivolol in human plasma.

关 键 词：奈比洛尔 LC-MS/MS 药代动力学 

分 类 号：R969.1[医药卫生—药理学]