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10mg,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0.3ng·mL^-1,在0.3-1000ng·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AUCo硼分别为(1032.6±204.6)ng·mL^-1和(1053.9±185.7)ng·mL^-1。两种制剂的主要药动学参数cmax,AUCo-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。
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 volun- teers 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 0.3ng·mL^-1 and the calibration curve was linear over the range of 0. 3 - 1000ng·mL^-1. The intra-and inter-run standard deviation was less than 15%. The t C tl/2, and AUCo-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^-l, (8.8±1.7) and (8.7±2.1) h, (1032.6±204.6) and ( 1053.9±185.7)ng·mL^-1, respectively. The relative bioavailability of the test product to the reference was 99.7±21.2%. Conclusion: The two formulations were bioequivalent.
出处
《药学与临床研究》
2007年第5期380-383,共4页
Pharmaceutical and Clinical Research