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目的建立一种简便、灵敏的测定受试者口服盐酸伐昔洛韦片受试制剂和参比制剂后的血药浓度的高效液相色谱-串联质谱(HPLC-MS/MS)方法,估算两种制剂的药动学参数并评价生物等效性。方法本试验采用双周期、随机、自身交叉试验设计,24名受试者服用受试制剂0.45 g或参比制剂0.5 g,两次用药间隔1周。阿昔洛韦血浆样品经30%三氟乙酸沉淀离心取上清液采用50%氨水中和后进样高效液相色谱-串联质谱(HPLC-MS/MS),以内标法计算阿昔洛韦血药浓度。分别计算受试制剂和参比制剂的药代动力学参数,利用Phoenix WinNonlin 6.1软件分析数据,以AUC、ρmax和tmax为指标进行人体生物等效性评价。结果受试制剂和参比制剂血浆中阿昔洛韦的ρmax分别为(3 457.92±783.83)和(4 181.25±1 130.19)μg.L-1,t1/2分别为(3.04±0.41)和(3.13%±0.52)h,AUC0-tn分别为(10 624.29±2 007.05)和(12 607.30±2 808.07)μg.h.L-1,受试制剂的F0-tn为(95.25±15.72)%,F0–∞为(95.32±15.76)%。结论本方法简便快速、灵敏准确,适用于阿昔洛韦在人体体内的药动学研究,统计结果表明,受试制剂和参比制剂等效。
OBJECTIVE To establish a simple and sensitive HPLC-MS / MS method for the determination of plasma concentrations of valaciclovir hydrochloride tablets and reference preparations after oral administration, Pharmacokinetic parameters of the formulations were evaluated and bioequivalence was evaluated. Methods The experiment was designed in a double-cycle, randomized, self-crossed trial. Twenty-four subjects took 0.45 g of the test preparation or 0.5 g of the reference preparation at intervals of one week between two doses. The acyclovir plasma samples were centrifuged with 30% trifluoroacetic acid and centrifuged to determine the concentration of acyclovir by HPLC-MS / MS using 50% aqueous ammonia followed by high performance liquid chromatography-tandem mass spectrometry Blood concentration. The pharmacokinetic parameters of the test preparations and the reference preparations were calculated respectively. The data were analyzed by using Phoenix WinNonlin 6.1 software and the bioequivalence of the human body was evaluated by AUC, ρmax and tmax. Results The plasma ρmax of acyclovir in the test and reference preparations were (3 457.92 ± 783.83) and (4 181.25 ± 1 130.19) μg.L-1, respectively, with t1 / 2 being (3.04 ± 0.41) and 3.13% ± 0.52) h and AUC0-tn were (10 624.29 ± 2 007.05) and (12 607.30 ± 2 808.07) μg.hL-1, respectively. The F0-tn was 95.25 ± 15.72% ∞ is (95.32 ± 15.76)%. Conclusion The method is simple and rapid, sensitive and accurate. It is suitable for the study of pharmacokinetics of acyclovir in human body. The statistical results show that the test and reference preparations are equivalent.