HPLC-MS/MS法测定人血浆中阿雷地平及其主要代谢产物的浓度  

Determination of aranidipine and its active metabolite in human plasma by HPLC-MS/MS

作　　者：赵桂平[1] 李静[1] 刘文芳[1] 吴伟[1] 张颖超[1] 林阳[1] 杨克旭[1] 仇琪[1] 所伟[1] 杜海燕[1] 周子杰[1] ZHAO Gui-ping;LI Jing;LIU Wen-fang;WU Wei;ZHANG Ying-chao;LIN Yang;YANG Ke-xu;QIU Qi;SUO Wei;DU Hai-yan;ZHOU Zi-jie(Institute of Clinical Pharmacology,Beijing Anzhen Hospital of Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院临床药理中心,北京100029

出　　处：《中国临床药理学杂志》2018年第24期2861-2864,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项基金资助项目(2017ZX09304017)

摘　　要：目的建立高效液相色谱-质谱联用法(HPLC-MS/MS)定量测定人血浆中阿雷地平及其主要代谢产物羟基阿雷地平的浓度。方法人血浆样品用液液萃取法处理,用Kinetex C_(18)柱(4. 6 mm×100 mm,2. 6μm)色谱柱,以纯水-乙腈溶液为流动相,流速为0. 5 mL·min^(-1),用电喷雾离子化源,负离子方式,多反应监测(MRM)扫描方式进行监测。考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果血浆中阿雷地平的标准曲线方程为y=4. 45×10^(-1)x+6. 6×10^(-3)(r=0. 998 2),在0. 02～10μg·L^(-1)线性关系良好,定量下限为0. 02μg·L^(-1);羟基阿雷地平的标准曲线方程为y=9. 82×10^(-1)x+1. 70×10^(-3)(r=0. 996 7),在0. 2～100μg·L^(-1)线性关系良好,定量下限为0. 2μg·L^(-1)。2种化合物的日内、日间RSD均<10%,提取回收率为91. 78%～97. 97%,无明显的基质效应。结论本法快速、准确、灵敏度高、重现性好,适用于人体血浆中阿雷地平、羟基阿雷地平浓度的测定,可用于阿雷地平、羟基阿雷地平的药代动力学研究。Objective To develop an high-performance liquid chroma- tography-tandem mass spectrometry HPLC-MS /MS) method for determination of aranidipineAR) and its active metabolite hydroxyl-aranidipine AR-M1) in human plasma. Methods The plasma samples were liquid-liquid extracted,then the supernatant were separated on Kinetex C18 4. 6 mm × 100 mm, 2. 6 mm) and eluted with water-ace- tonitrile solution,the flow rate was 0. 5 mL min-1 . Detection of the an- alyte was achieved using negative ion electrospray ionization ESI) in the multiple reaction monitoring MRM) mode. The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were examined. Results The linear regression curve of aranidipine was y = 4. 45 × 10-1 x + 6. 6 × 10-3 r = 0. 998 2) ,the linear range was 0. 02-10μg·L^-1 ,with the lower limit of quantitation LLOQ) of 0. 02μg·L^-1 . The linear regression curve of hydroxyl-aranidipine was y = 9. 82 × 10-1 x + 1. 70 × 10-3 r = 0. 996 7) ,the linear range was 0. 2-100 μg·L^-1,with the LLOQ of 0. 2μg·L^-1. Intra-day and inter-day relative standard deviations of two analytes were both below 10%. The absolute recovery in plasma was 91. 78%-97. 97%,and no significant matrix effect was found. Conclusion The method is rapid,accurate,sensitive,and reliable. It is suitable for the determination of the concentrations of aredipine and hydroxyl-aredipine in human plasma. It can be used for aredipine and hydroxyl-aredipine with pharmacokinetic study.

关 键 词：阿雷地平 羟基阿雷地平 高效液相色谱-质谱联用(HPLC-MS/MS) 血浆药物浓度 

分 类 号：R972[医药卫生—药品]