中国药房2013，Vol.24Issue(1)：49-51,3.DOI:10.6039/j.issn.1001-0408.2013.01.17
LC-MS/MS法测定大鼠血浆中维拉帕米与其代谢产物去甲维拉帕米的浓度及其药动学研究
Determination of Verapamil and Its Metabolite Norverapamil in Rats Plasma by LC-MS/MS and Its Pharmacokinetics Study
郑侠 1刘昌辉 2王宁生 1宓穗卿1
作者信息
- 1. 广州中医药大学临床药理研究所,广州 510405
- 2. 广东省医学实验动物中心,广东佛山528248
- 折叠
摘要
Abstract
OBJECTIVE: To establish a method for determining concentrations of verapamil (Ver) and its metabolite norverapamil (Nor) in rat plasma and to study its pharmacokinetics. METHODS: After intragastrical administration of Ver 10 mg/kg in 6 rats, the plasma concentrations of Ver and Nor were determinaed by LC-MS/MS within 24 h before and after medication using tamoxifen as internal standard. The pharmacokinetic parameters were calculated by 3p97 software. The determination was performed on Alltima C18 column with mobile phase consisted of methanol-0.05% formic acid (gradient elution) with column temperature of 40 ℃. The LC-MS/MS system was operated using an electrospray ionization; the ion of monitor: m/z 455.3/165.0 (Ver), 441.0/ 165.0 (Nor) and 372.2/129.1 (tamoxifen). RESULTS: The linear ranges of Ver and Nor were 2-1 000 ng/ml (rVer=0.999 4,rNor= 0.999 2) , and the lowest limit of quantification was 0.5 ng/ml. The pharmacokinetics parameters were as follows: Cmax: (669.91 ± 80.99) vs. (681.86±79.79) ng/ml; t1/2: (2.26±0.31) vs.(2.44±0,29) h; AUC0-∞: (1 331.33± 165.20) vs. (2 341.661201.20) ng· h/ml. CONCLUSIONS: The method is proved to be specific, sensitive and accurate, and suitable for the determination of Ver and Nor concentration in plasma. The pharmacokinetics of them in rats are in line with two-compartment model.关键词
维拉帕米/去甲维拉帕米/大鼠/液相色谱-串联质谱法/药动学Key words
Verapamil/ Norverapamil/ Rats/ LC-MS/MS/ Pharmacokinetics分类
医药卫生引用本文复制引用
郑侠,刘昌辉,王宁生,宓穗卿..LC-MS/MS法测定大鼠血浆中维拉帕米与其代谢产物去甲维拉帕米的浓度及其药动学研究[J].中国药房,2013,24(1):49-51,3.
