液相色谱-串联质谱法测定人血浆中厄贝沙坦  被引量:6

Determination of Irbesartan in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry

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作  者:关心[1] 陈笑艳[2] 宋波[2] 张逸凡[2] 钟大放[2] 

机构地区:[1]沈阳药科大学药物代谢与药动学实验室,沈阳110016 [2]中国科学院上海药物研究所药物代谢研究中心,上海201203

出  处:《中国药学杂志》2007年第19期1486-1489,共4页Chinese Pharmaceutical Journal

摘  要:目的建立快速、灵敏的液相色谱-串联质谱法测定人血浆中厄贝沙坦的浓度。方法50μL血浆样品经乙腈沉淀蛋白处理后,以乙腈-水-甲酸(90:10:0.25)为流动相,Zorbax SB C18柱分离,通过电喷雾离子源四极杆串联质谱,以选择反应监测(SRM)方式进行检测。结果测定血浆中厄贝沙坦方法的线性范围为2.0~5000μg·L^-1定量下限为2.0μg·L^-1。日内、日间精密度(RSD)均小于8.3%,准确度(RE)在±4.1%以内,厄贝沙坦和内标替米沙坦的回收率分别为90.9%和90.4%:每个样品测试时间仅为3.6min.用此法研究了18名健康受试者单剂量po150mg厄贝沙坦片后的药动学特点。结论该法选择性强,灵敏度高,适用于厄贝沙坦的临床药动学研究。OBJECTIVE To develop a LC/MS-MS method for direct quantification of irbesartan in human plasma. METHODS An aliquot of 50 μl, plasma was treated by a simple protein precipitation using acetonitrile, then separated on a Zorbax SB C18 column. The mobile phase consisted of acetonitrile-water-formie acid (90: 10: 0. 25). A triple quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) mode using the precursor to product ion of m/z 429 to m/z 207 and m/z 515 to m/z 276 was performed to quantify irbesartan and the internal standard telmisartan, respectively. RESULTS The linear calibration curves were obtained irl the concen- tration range of 2.0-5 000 μg·L^-1. The lower limit of quantification was 2. 0 μg · L^-1. The inter- and intra-day precision (RSD) was below 8. 3%, and the accuracy (RE) was within ± 4. 1% calculated from QC samples. The method gave the mean recovery 90. 9% and 90.4% to irbesartan and internal standard telmisartan, respectively. The total chromatographic run time was only 3.6 min. The method was employed in a pharmacokinetic study of irbesartan after an oral administration to 18 healthy volunteers. CONCLU- SION The method was proved to be selective, sensitive, and suitable for clinical investigation of irbesartan pharmacokinetics.

关 键 词:液相色谱-串联质谱法 厄贝沙坦 药动学 血浆药物浓度 

分 类 号:R971[医药卫生—药品]

 

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