LC-MS/MS法测定人血浆中的依地普仑及其药动学研究

目的:建立人血浆中依地普仑浓度的LC-MS/MS测定方法,并研究其在健康人体内的药动学特征.方法:以吲哒帕胺为内标,色谱柱:Inspire-C18(150 mm×4.6 mm,5 μm,Dikma),流动相:甲醇-10 mmol·L-1的醋酸铵水溶液(含0.1%甲酸)(85:15),流速:0.6 ml·min-1;质谱检测依地普仑和内标吲哒帕胺离子对分别为m/z 325.2→109.1,366.1→132.1.20名健康受试者分成两组,分别进行低(10 mg)、高(20 mg)单次给药,其中低剂量单次给药结束后继续进行多次给药的药动学试验.结果:依地普仑的线性范围为0.102 1～102.1 ng·ml-1(r=0.999,n=5),定量下限为0.102 1 ng·ml-1,提取回收率>82.9%,日内和日间RSD≤4.2%.依地普仑单剂量给药后t1/2分别为(47.42±7.87)和(41.51±6.34)h;tmax分别为(5.70±1.64)和(5.50±2.37)h;Cmax分别为(15.35±2.71)和(34.39±2.16)ng·ml-1;AUC0-144分别为(723.61±191.77)和(1 683.37±242.29)ng·h·ml-1;呈线性动力学特征.多剂量给药后Cmax为(16.60±4.21)ng·ml-1;AUCss为(253.89±44.22) ng·h·ml-1;Cav为(10.58±1.84) ng·ml-1和DF(0.95±0.19).结论:该方法适用于依地普仑血药浓度测定及人体药动学研究.

Determination of Escitalopram in Human Plasma by LC-MS/MS and Resarch of Pharmacokinetics in Healthy Chinese Volunteers

Objective： To establish an LC-MS/MS method for the determination of escitalopramin in human plasma and investigate the pharmacokinetic characteristics in healthy Chinese subjects.Method： The chromatographic separation was achieved on an Inspirel C18 column（150 mm×4.6 mm,5 μm,Dikma） using a mixture of methanol and 10 mM ammonium acetate buffer containing 0.1% formic acid（85∶ 15） as the mobile phase at the flow rate of 0.6 ml·min-1.MS was performed in the selected reaction monitoring mode using target ions at m/z 325.2→109.1 for escitalopramin and m/z 366.1→132.1 for internal standard.Twenty subjects were divided into two groups with 10 and 20 mg single dose escitalopramin,respectively.The 10 mg group continued multiple-dose pharmacokinetic experiments.Result： The assay for escitalopramin in plasma showed good linearity（r≥0.99） over the range of 0.102 1-102.1 ng·ml-1.The extraction recovery was above 82.9% and both the intra-day and inter-day precision were less than 4.2%.Escitalopramin displayed linear PK properties in the tested doses.The pharmacokinetic parameters for 10 and 20 mg single dose of escitalopram tablets were as follows：t1/2 of（47.42±7.87） and（41.51±6.34）h,tmax of（5.70±1.64） and（5.50±2.37）h,Cmax of（15.35±2.71） and（34.39±2.16）ng·ml-1,AUC（0-144） of（723.61±191.77） and（1 683.37±242.29）ng·h·ml-1.The pharmacokinetic parameters for 10 mg multiple-dose escitalopram tablets were as follows： Cmax of（16.60±4.21） ng·ml-1,AUCss of（253.89±44.22） ng·h·ml-1,Cav of（10.58±1.84） ng·ml-1 and DF of（0.95±0.19）.Conclusion： The method can be successfully used in the clinical pharmacokinetic study of escitalopram.