液相色谱-串联质谱法测定人血浆苯磺酸氨氯地平与阿托伐他汀钙浓度

Determination of Amlodipine Besylate and Atorvastatin Calcium in Human Plasma by LC-MS/MS

目的建立同时测定人血浆苯磺酸氨氯地平与阿托伐他汀钙的液相色谱-串联质谱(LC-MS/MS)检测方法。方法以尼莫地平为内标,血浆样品采用甲基叔丁基醚提取,色谱柱为Agilent TC-C18柱(150mm×4.6mm,5μm),流动相为乙腈:5.0mmol·L-1醋酸铵缓冲液(pH值=4.0)(25:75,V/V);流速0.25mL·min-1;苯磺酸氨氯地平、阿托伐他汀钙和内标尼莫地平分别选择m/z409.1→238.0,559.2→440.2,419.1→343.1。结果苯磺酸氨氯地平与阿托伐他汀钙在0.05～20.00μg·L-1范围内均线性关系良好,加样浓度分别为0.1,2.0,18.0μg·L-1时,样品提取回收率分别为76.78%,77.08%,76.27%与80.16%,79.69%,81.82%,日内和日间RSD均<15%。结论该方法灵敏度高,操作简便、快速,适用于苯磺酸氨氯地平与阿托伐他汀钙临床药动学的研究。

Objective To establish a sensitive and selective LC-MS/MS method for the simultaneous determination of amlodipine besylate and atorvastatin calcium in human plasma. Methods The plasma samples were extracted by methyl tert-butyl ether with nimodipine as internal standard. Separation was achieved on an Agilent TC-C18 reversed-phase column with a mobile phase composed of acetonitrile-5.0 mmol·L-1 ammonium acetate buffer （pH4.0） （25：75,V/V） at a flow rate of 0.25 mL·min-1. The mass transition pairs of m/z 409.1→238.0,559.2→440.2,and 419.1→343.1 were used to detect amlodipine besylate,atorvastatin calcium and internal standard. Results The assay was linear over the concentration range 0.05-20.0 μg·L-1 for amlodipine besylate and atorvastatin calcium in human plasma. Recoveries at concentrations 0.1,2.0 and 18.0 μg·L-1 for amlodipine besylate were 76.78%,77.08% and 76.27%,and for atorvastatin calcium were 80.16%,79.69% and 81.82%,respectively. The method was accurate with all intra- and inter-day mean concentrations within 15% of nominal values at 0.1,2.0 and 18.0 μg·L-1. Conclusion This method was robust and suitable for clinical pharmacokinetic studies of amlodipine besylate and atorvastatin calcium.