伊伐布雷定及去甲伊伐布雷定的血药浓度测定及初步药动学研究.pdfVIP

·2800 · 中华临床医师杂志( 电子版)2014 年8 月第8 卷第15 期 Chin J Clinicians(Electronic Edition),August 1,2014,Vol.8,No.15 ·临床论著· 伊伐布雷定及去甲伊伐布雷定的血药 浓度测定及初步药动学研究 王娜 宋冬梅 张振秋 钟丽丽 刘洋 刘婷立 【摘要】 目的 建立高效液相色谱-质谱 （HPLC-MS/MS ）法测定人血浆中伊伐布雷定及去甲 伊伐布雷定浓度并用于人体药动学研究。方法 血浆样品处理均采用乙腈沉淀蛋白法，以地西泮为 内标。质谱条件均采用电喷雾离子源（ESI ）、正离子和多反应离子监测（MRM ）模式进行检 测。结果 本方法伊伐布雷定线性范围为0.096 7～145.050 0 ng/ml，r ＝0.997 1，最低定量浓度为 0.096 7 ng/ml，去甲伊伐布雷定线性范围为0.050 5～30.270 0 ng/ml，最低定量浓度为0.050 5 ng/ml， r ＝0.997 5 。两者日内、日间RSD 均＜15%。提取回收率为＞78.5 % 。结论 该方法简单、灵敏、可 靠，适用于伊伐布雷定及去甲伊伐布雷定人体药动学研究。 【关键词】 伊伐布雷定； 去甲伊伐布雷定； 血药浓度； 药代动力学； 液相色谱-质谱 法 Determination of Ivabradine and N-desmethylivabradine concentration in human plasma by * * HPLC-MS/MS Wang Na , Song Dongmei, Zhang Zhenqiu, Zhong Lili, Liu Yang, Liu Tingli. Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China Corresponding author: Song Dongmei, Email: elainesong@ 【Abstract 】 Objective To establish HPLC-MS/MS methods to detemine the concentration of Ivabradine and N-desmethylivabradine in human plasma and investigate their pharmacokinetics in humans. Methods An internal standard (Diazepam) and sedimentation process with acetonitrile were used for determining the plasma concentration of both Ivabradine and N-desmethylivabradine. The multiple reaction monitor (MRM) with positive mode and electrospray ionization source (ESI) was used. Results The concentration of Ivabradine and N-desmethylivabradine in the plasma showed a good linearity at 0.096 7- 145.050 0 ng/ml (r=0.997 1) and 0.050 5-30.270 0 ng/ml respectively (r=0.997 5). The minimum quantitative concentration were 0.096 7 ng/ml and 0.050 5 ng/ml, respectively.