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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,5μm,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。
Objective: To establish a method for the determination of escitalopram in human plasma by LC-MS / MS and study its pharmacokinetics in healthy volunteers. Methods: Indapamide was used as the internal standard. The chromatographic column was Inspire-C18 (150 mm × 4.6 mm, 5 μm, Dikma). The mobile phase was methanol-10 mmol·L-1 aqueous solution of ammonium acetate (85:15) at a flow rate of 0.6 ml · min-1. The plasma ion-pair spectra of escitalopram and indapamide were m / z 325.2 → 109.1, 366.1 → 132.1.20, respectively. The healthy subjects were divided into The two groups were given a single dose of low (10 mg) and high (20 mg) respectively, and the pharmacokinetic test was repeated after the single dose of low dose was completed. The results showed that the linear range of escitalopram was 0.102 1 ~ 102.1 ng.ml-1 (r = 0.999, n = 5), the lower limit of quantification was 0.102 1 ng.ml-1, the recovery rate was> 82.9% RSD ≤ 4.2%. The values of tmax were (5.70 ± 1.64) and (5.50 ± 2.37) h, respectively, and the values of Cmax were (15.35 ± 2.71) and (31.51 ± 6.34) ) And (34.39 ± 2.16) ng.ml-1, respectively; AUC0-144 was (723.61 ± 191.77) and (1 683.37 ± 242.29) ng.h.ml-1, respectively. The Cmax after multi-dose administration was (16.60 ± 4.21) ng.ml-1, AUCss was (253.89 ± 44.22) ng.h.ml-1, Cav was (10.58 ± 1.84) ng.ml- 0.19). Conclusion: This method is suitable for the determination of aldendron blood concentration and human pharmacokinetic study.