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  

Determination of Ivabradine and N-desmethylivabradine concentration in human plasma by HPLC-MS/MS

作　　者：王娜[1] 宋冬梅[2] 张振秋[1] 钟丽丽[2] 刘洋[2] 刘婷立[2] 

机构地区：[1]辽宁中医药大学,沈阳110032 [2]沈阳亿灵医药科技有限公司

出　　处：《中华临床医师杂志（电子版）》2014年第15期27-31,共5页Chinese Journal of Clinicians(Electronic Edition)

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0.0967～145.0500 ng/ml，r＝0.9971，最低定量浓度为0.0967 ng/ml，去甲伊伐布雷定线性范围为0.0505～30.2700 ng/ml，最低定量浓度为0.0505 ng/ml， r＝0.9975。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。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. The intra-day and inter-day precisions were lower than 15% （RSD）. The recovery was higher than 78.8% in each QC sample. Conclusion The methods is simple, sensitive and accurate for the study on pharmacokinetic of Ivabradine and N-desmethylivabradine in human.

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 

分 类 号：R96[医药卫生—药理学]