UHPLC-MS/MS法同时测定人血浆中氨氯地平和缬沙坦的质量浓度  

Simultaneous determination of amlodipine and valsartan in human plasma by UHPLC-MS/MS

作　　者：臧亚楠 马婷婷 王鑫[1] 刘有平[1] 邸欣[1] ZANG Yanan;MA Tingting;WANG Xin;LIU Youping;DI Xin(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Quarkman Pharmaceutical Technology Company Limited of Liaoning,Benxi 117004,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]夸克侠医药科技(辽宁)有限公司,辽宁本溪117004

出　　处：《沈阳药科大学学报》2019年第10期887-893,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立快速、灵敏的UHPLC-MS/MS法同时测定人血浆中氨氯地平和缬沙坦的质量浓度,并将此方法应用于缬沙坦氨氯地平单片复方制剂的人体药物动力学研究。方法采用氘代同位素双内标(缬沙坦-d3和氨氯地平-d4),血浆样品采用乙腈沉淀蛋白结合样品稀释的方法进行预处理,色谱柱为Waters Xbridge-C18柱(50 mm×2.1 mm,2.5μm),流动相为水(含体积分数为0.1%的甲酸)-甲醇(含体积分数为0.1%的甲酸),梯度洗脱,流速为0.4 mL·min^-1。离子源为电喷雾电离(ESI)源,正离子化方式,扫描方式为多反应离子监测(MRM)。结果血浆中氨氯地平和缬沙坦的质量浓度分别在0.1~20.0μg·L-1和2.0~5000μg·L^-1内线性关系良好,提取回收率分别为89.1%~92.8%和95.5%~103.1%,方法的专属性、精密度和准确度均符合测定要求。结论该方法适用于缬沙坦氨氯地平单片复方制剂在人体内的药代动力学研究。Objective To develop a rapid and sensitive UHPLC-MS/MS method for simultaneous determination of amlodipine and valsartan in human plasma and to investigate the pharmacokinetics of amlodipine and valsartan combination tablet in healthy human subjects.Methods Using valsartan-d3 and amlodipine-d4 as internal standards,plasma samples were pretreated by protein precipitation with acetonitrile followed by a two-fold dilution with 0.1%formic acid-water.The analyte and the internal standards were separated by HPLC on a C18 column using water-methanol containing 0.1%formic acid as gradient mobile phase at a flow of 0.4 mL·min-1.Mass detection was conducted by multiple reaction monitoring(MRM)via positive electrospray ionization.Results The method was fully validated and proved to be linear in the ranges of 0.1-20.0μg·L^-1 for amlodipine and 2.0-5000μg·L^-1 for valsartan.The extraction recoveries for amlodipine and valsartan ranged from 89.1%to 92.8%and 95.5%to 103.1%,respectively.The specificity,intra-and inter-day precisions and matrix effects met the requirements for bioanalytical method validation.Conclusion The method is simple,rapid,sensitive and accurate,and can be applied to pharmacokinetic study of amlodipine and valsartan combination tablet in human.

关 键 词：缬沙坦 氨氯地平 血浆 药物动力学 超高效液相色谱-串联质谱法 

分 类 号：R969[医药卫生—药理学]