人血浆中盐酸马尼地平的LC-MS法测定及药动学

Determination of Manidipine Hydrochloride in Human Plasma by LC-MS and Its Pharmacokinetics

建立了LC-MS法测定人血浆中盐酸马尼地平的浓度,并研究了12名健康志愿者单剂量和多剂量口服盐酸马尼地平后的药物动力学。以尼莫地平为内标,采用Venusil XBP C8色谱柱,5mmol/L乙酸铵溶液(含0.5%乙酸)-甲醇-乙腈(15∶40∶45)为流动相,流速0.6ml/min,血浆样品经乙酸乙酯萃取。AP-ESI离子源,正离子模式,采集离子马尼地平为611.4(M+1)和尼莫地平为441.1(M+Na)。盐酸马尼地平在0.25～50ng/ml浓度范围内线性关系良好,方法回收率和提取回收率分别大于99%和49%,日内、日间RSD均小于8%。

A LC-MS method was established for the determination of manidipine hydrochloride in human plasma. Pharmacokinetics after single dose and multi dose oral administration of manidipine hydrochloride in 12 healthy volunteers were discussed. The analytes were extracted by ethyl acetate and nimodipine was used as internal standard. A Venusil XBP C8 column was used, with mobile phase of 5 mmol/L ammonium acetate solution （containing 0.5% acetic acid）-methanol-acetonitrile （15 ： 40 ： 45）. The flow rate was 0.6ml/min. Atmospheric pressure electronic spray ionization （AP-ESI）was used, and it was operated in the positive ion mode. Selected ion monitoring ions were 611.4 （M＋ 1） for manidipine and 441.1 （M＋Na） for nimodipine, respectively. The calibration curve of manidipine hydrochloride was linear in the concentration range of 0.25 - 50ng/ml. The recovery and extraction recovery were more than 99 % and 49 %, respectively. The RSDs of intra- and inter-day were less than 8 %.