LC-MS/MS快速测定人血浆中氯沙坦浓度及其生物等效性研究

Rapid determination of losartan in human plasma by LC-MS/MS and study on its bioequivalence

目的建立人血浆中氯沙坦LC-MS/MS测定方法,计算氯沙坦人体药动学参数并评价两制剂生物等效性。方法采用单剂量双周期交叉试验设计,完成试验的23例受试者空腹口服受试或参比制剂氯沙坦钾片100 mg后,用甲醇一步沉淀血浆蛋白,并用LC-MS/MS法测定人血浆中氯沙坦浓度。用DAS 3.2.3软件计算氯沙坦人体药动学参数,并评价两制剂生物等效性。结果服用受试和参比制剂后,血浆中氯沙坦的Cmax分别为(697.3±301.7)和(674.1±350.5)ng/m L,AUC0-12 h分别为(994±240)和(1 005±287)ng·h/m L,tmax分别为(1.23±0.38)和(1.37±0.75)h,t1/2分别为(2.04±0.28)和(2.00±0.40)h,生物利用度为102.4%±21.1%。结论建立的分析测试方法灵敏、简便、准确,受试制剂与参比制剂生物等效。

Objective To establish an LC-MS/MS method for the determination of losartan in human plasma, and evaluate the bioequivalence of losartan potassium tablet in healthy volunteers. Methods A single oral dose of test and reference formulations was given to 23 healthy male volunteers according to a randomized crossover design. Plasma concentration was determined by LC-MS/MS after deproteinized with methanol. The pharmacokinetic parameters were calculated by DAS 3.2. 3. Results The main pharmacokinetic parameters of losartan in test and reference preparations were as follows ： Cmax （ 697. 3 ± 301.7 ） and （ 674. 1 ±350. 5 ） ng/mL, AUC0-12 h （ 994 ± 240 ） and （ 1 005 ± 287 ）mg· h/ mL, tmax （ 1.23 ± 0. 38 ） and （ 1.37 ± 0. 75 ） h, tl/2 （ 2.04± 0. 28 ） and （ 2. 00 ±0.40 ） h, respectively. The relative bio- availability of test formulations was 102. 4% ± 21.1%. Conclusion LC-MS/MS method is proved to be sensitive, convenient and accurate. Losartan potassium tablet is bioequivalent to the reference tablet.