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目的建立大鼠血浆中维生素K_1的高效液相色谱测定法,并应用于经灌胃给予维生素K_1微乳剂后的维生素K_1药动学研究。方法大鼠经灌胃给予维生素K,微乳剂3.77 mg·kg~(-1),于给药后不同时间采集血样,采用无水乙醇-乙醚(体积比为1:3)提取的方法处理血浆样品。采用反相高效液相色谱法测定维生素K_1的血药浓度,色谱柱为Thermo C_(18)柱(150 mm×4.6 mm,5μm),流动相为无水乙醇-水(体积比为90:10),流速为1.1 mL·min~(-1),检测波长为270 nm,柱温为35℃。结果血液中的内源性物质不干扰测定。维生素K_1的线性为48～2 400μg·L~(-1),r=0.995 3,定量下限为48μg·L~(-1),精密度、准确度、回收率均符合生物样品测定要求。主要药物动力学参数:t_(max)=1.0 h,t_(1/2)=7.61 h,ρ_(max)=0.77 mg·L~(-1),AUC_(0-t)=2.87 mg·h·L~(-1),AUC_(0-∞)=3.21 mg.h·L~(-1)。结论该方法适用于维生素K,微乳剂在大鼠体内的药物动力学研究。
OBJECTIVE To establish a method for the determination of vitamin K_1 in plasma of rats and to study the pharmacokinetics of vitamin K_1 after oral administration of vitamin K_1 microemulsion. Methods The rats were given vitamin K and microemulsion 3.77 mg · kg -1 by intragastric administration. Blood samples were collected at different time points after administration. The plasma was extracted with absolute ethyl alcohol (1: 3 by volume) sample. The HPLC method was used to determine the plasma concentration of vitamin K_1. The column was Thermo C 18 column (150 mm × 4.6 mm, 5 μm) and the mobile phase was absolute ethanol-water (volume ratio 90:10 ), The flow rate was 1.1 mL · min ~ (-1), the detection wavelength was 270 nm and the column temperature was 35 ℃. As a result endogenous substances in the blood do not interfere with the assay. The linear range of vitamin K_1 was 48-2 400 μg · L -1, r = 0.995 3, and the lower limit of quantitation was 48 μg · L -1. The precision, accuracy and recovery of vitamin K_1 were in accordance with the requirements of biological samples. The main pharmacokinetic parameters were as follows: t max = 1.0 h, t 1/2 = 7.61 h, ρ max = 0.77 mg · L -1, AUC 0-t = 2.87 mg · h · L -1, AUC 0 -∞ = 3.21 mg.h · L -1. Conclusion This method is suitable for the pharmacokinetics of vitamin K and microemulsion in rats.