硝苯地平对美托洛尔大鼠体内药动学的影响  

Effect of nifedipine on pharmacokinetics of metoprolol in rats

作　　者：刘茜[1] 褚雨[1] 赵辉[1] 邵馨[1] 张旭[1] 刘艳芳[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2011年第12期995-999,共5页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立一种LC-MS/MS法测定大鼠血浆中美托洛尔的浓度,研究硝苯地平对美托洛尔在大鼠体内药动学的影响。方法采用C18柱分离,用普萘洛尔作内标,流动相:乙腈-水-甲酸(体积比为40.0∶60.0∶0.1),用乙酸乙酯提取处理,采用ESI源,正离子方式检测,扫描方式为多反应监测(multiple reaction monitoring,MRM)。结果单独给药组与联合给药组主要药动学参数如下:ρmax分别为(502.8±67.0)和(623.8±137.3)μg.L-1,tmax分别为(0.50±0.08)和(0.58±0.13)h,t1/2分别为(1.25±0.80)和(1.53±0.58)h,AUC0-t分别为(442.8±50.9)和(730.8±218.2)μg.h.L-1,MRT0-t分别为(1.24±0.14)和(1.68±0.41)h,Cl/F分别为(39.0±3.41)和(25.4±7.46)L.h-.1kg-1,AUC0-t、MRT0-t、Cl/F具有显著性差异(P<0.05),其他药动学参数无显著性差异(P>0.05)。结论硝苯地平影响美托洛尔在大鼠体内吸收和消除的药动学过程。Objective To develop an LC-MS/MS method for the quantification of metoprolol in rat plasma for investigating the interactive effects of nifedipine to metoprolol in rat plasma. Methods Mobile phase consisted of a mixture of acetonitrile-water-formic acid（ V： V： V =40. 0： 60. 0： 0. 1 ）was used for the separation. Internal standard was propranolol, the extraction was performed by ethyl acetate and the samples were analyzed on C18 column. The ion source was adopted positine ion and multiple reaction monitoring（MRM）. Resuits The pharmacokinetic parameters of metoprolol in rats after the i. g. administration of metoprolol alone and the combination of metoprolol and nifedipine were as follow pmax were （502. 8 ± 67.0 ） and （623.8 ± 137.3）μg·L^-1 ,tmax were（0. 50 ＋0. 08） and（0. 58 ±0. 13）h,t1/2 were（ 1.25 ±0. 80） and（ 1.53 ±0. 58）h, AUC0-t, were （442.8 ± 50. 9 ） and （ 730. 8 ± 218.2 ） μg. h. L ^-1, MRT0-t were （ 1.24± 0. 14 ） and （ 1.68± 0. 41 ） h, C1/F were （ 39. 0 ± 3.41 ） and （ 25.4 ± 7.46 ） L. h^-1. kg ^-1. AUC0-t MRT0-t, CI/F showed significance difference with each other（ P 〈 0. 05 ）, there were no significant differences of the other pharmacokinetic parameters（P 〉 0. 05 ）. Conclusions This method is sensitive and stable. The absorption and elimination of metoprolol in rats were effected by nifedipine.

关 键 词：美托洛尔 硝苯地平 高效液相色谱-串联质谱 药动学 

分 类 号：R917[医药卫生—药物分析学]