LC-MS/MS法测定人血浆中甲磺酸雷沙吉兰片浓度及其药动学研究

目的:建立测定人血浆中甲磺酸雷沙吉兰的液相色谱-串联质谱色谱法（LC-MS/MS）,研究甲磺酸雷沙吉兰在健康人体内的药物动力学特征。方法:采用LC-MS/MS测定人血浆中甲磺酸雷沙吉兰浓度,选择监测的离子为m/z 172→117.15（甲磺酸雷沙吉兰）和m/z 340.1→324.1（罂粟碱）。色谱柱为Inertsil ODS-3色谱柱（250 mm×4.6 mm,5μm）;流动相:甲醇-（0.2%醋酸胺+0.25%氨水）（85:15）。结果:雷沙吉兰在0.010～40 ng·ml^-1浓度范围内呈良好的线性关系（r=0.999 5）,最低检测浓度为0.010 ng·ml^-1,应用此法测得0.5、1.0、2.0 mg剂量组不同给药方式、多个时间点的雷沙吉兰血药浓度,结果呈线性动力学特征。结论:该方法灵敏度高、专属性强、准确、简便,适用于甲磺酸雷沙吉兰片的人体药动学研究。

Study on Determination of Rasagiline Mesylate in Human Plasma and its Pharmacokinetics by LC-MS/MS

Objective： To determine the concentration of rasagiline mesylate in human plasma by LC-MS/MS and to study its pharmacokinetics. Method： The chromatographic separation was performed on an Inertsil ODS-3 C18 column （250 mm×4. 6 mm, 5 μm） with mobile phase of methanol-0. 2% ammonium acetate solution and 0. 25% ammomia （85： 15）. Analysis was detected by LC-MS/MS under the following conditions： m/z 172 （precursor ion） to 117. 15 （product ion） for rasagiline mesylate and m/z 340. 1 （precursor ion） to 324. 1 （product ion）for the internal standard （papaverine）. Result： The standard curve was linear （r = 0. 999 5 ） within the concentration range of 0. 010-40 ng· ml-1. The lowest quantitative limit for rasagiline mesylate was 0. 010 ng·ml-1. The linear pharmacokinetics was detected in plasma concentration of the single oral dose of 0. 5,1.0 and 2.0 mg in the health volunteers. Conclusion： A rapid, sensitive and simple LC-MS/MS method for determination of rasagiline mesylate was developed, and the assay was successfully applied in clinical pharmacokinetic study.