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目的建立液相色谱-串联质谱法(LC-MS/MS)测定受试者口服氯沙坦钾片受试制剂和参比制剂后的血药浓度,估算两制剂的药动学参数并评价生物等效性。方法采用随机、开放、双周期交叉试验设计,20名中国男性健康受试者单剂量口服受试制剂和参比制剂50 mg后,血浆样品经甲醇直接沉淀蛋白后进行LC-MS/MS分析,利用DAS2.0软件计算药动学参数,并进行生物等效性评价。结果受试制剂和参比制剂血浆中氯沙坦的ρmax分别为(222±131)和(226±166)μg·L-1,tmax分别为(1.28±0.64)和(1.45±0.70)h,t1/2分别为(1.91±0.32)和(1.90±0.37)h,AUC0-12 h分别为(450±191)和(446±227)μg.h.L-1,相对生物利用度为(104.0±14.3)%。结论 建立的分析方法准确、灵敏、简便,统计结果表明,受试制剂和参比制剂生物等效。
OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the determination of plasma concentrations of losartan potassium tablets and reference preparations after oral administration of losartan potassium tablets. The pharmacokinetic parameters of the two formulations were estimated and evaluated Equivalence. Methods A randomized, open and double-cycle crossover design was used. The plasma samples were directly precipitated by methanol and analyzed by LC-MS / MS after the single oral dose of 50 mg and the reference formulation of 20 Chinese male healthy subjects were tested. Pharmacokinetic parameters were calculated using DAS 2.0 software and bioequivalence was evaluated. Results The pmax of losartan in the plasma of test and reference preparations were (222 ± 131) and (226 ± 166) μg · L-1, respectively, with tmax of 1.28 ± 0.64 and 1.45 ± 0.70 h, The relative bioavailability was (104.0 ± 14.3) days after the onset of AUC0-12 h (450 ± 191) and (446 ± 227) μg.hL-1, respectively )%. Conclusion The established analytical method is accurate, sensitive and simple. The statistical results show that the test preparation and the reference preparation are bioequivalent.