【摘要】 目的:建立人血浆中维生素K1浓度的HPLC-APCI-MS测定方法,并评价维生素K1软胶囊的药动学特征及其与维生素K1片剂的人体生物等效性。方法:20名男性健康受试者随机分成2组,分别交叉口服受试制剂和参比制剂各10 mg,采用HPLC-APCI-MS法测定人血浆中维生素K1的浓度,估算维生素K1的药动学参数及两种制剂的人体生物等效性。结果:血浆中维生素K1的最低定量限为0.3 ng.mL-1,在0.3~1000 ng.mL-1范围内线性关系良好,批内及批间精密度RSD均小于15%。受试制剂与参比制剂的各主要药动学参数:tmax分别为(5.5±0.8)h和(5.0±0.8)h,cmax分别为(210.1±86.7)ng.mL-1和(194.8±60.6)ng.mL-1,t1/2分别为(8.8±1.7)h和(8.7±2.1)h,用梯形法计算AUC0~48分别为(1032.6±204.6)ng.h.mL-1和(1053.9±185.7)ng.h.mL-1。两种制剂的主要药动学参数cmax,AUC0~48经对数转换后进行方差分析及双单侧t检验,并计算90%置信区间,表明两种制剂生物等效,相对生物利用度为(99.7±21.2)%。结论:两种制剂生物等效。更多还原

【Abstract】 Objective:To establish an HPLC-APCI-MS method for the determination of vitamin K1 in human plasma and to evaluate the pharmacokinetics and bioequivalence of vitamin K1 soft capsule and vitamin K1 tablet in healthy volunteers.Methods: A 10 mg dose of the reference or test drug was given to 20 healthy male volunteers in a randomized two-way crossover design and the plasma concentration of the drug was assayed by HPLC-MS.The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated.Results: The LOQ of the HPLC-APCI-MS method for vitamin K1 in plasma was 0.3 ng·mL-1 and the calibration curve was linear over the range of 0.3~1000 ng·mL-1.The intra-and inter-run standard deviation was less than 15%.The tmax,cmax,t1/2,and AUC0～48 of the test and reference drugs were(5.5±0.8) and(5.0±0.8) h,(210.1±86.7) and(194.8±60.6) ng·mL-1,(8.8±1.7) and(8.7±2.1) h,(1032.6±204.6) and(1053.9±185.7) ng·h·mL-1,respectively.The relative bioavailability of the test product to the reference was 99.7±21.2%.Conclusion: The two formulations were bioequivalent.更多还原