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目的:建立高效液相色谱测定大鼠血浆中橙黄决明素含量的方法,研究橙黄决明素在大鼠体内的药动学过程。方法:橙黄决明素灌胃给药7.2 mg·kg-1后于5,10,20,30 min及1,2,3,4,6,8,10,12,16,24 h断尾取血,液-液萃取法处理血浆样品,HPLC测定血浆中橙黄决明素浓度,以3P97软件拟合药动学参数。结果:血浆中橙黄决明素在0.12~7.62μg·ml-1线性良好,相关系数为0.999 5(n=5),低、中、高浓度萃取回收率均>95%,日内、日间RSD均<10%,符合要求。灌胃给药后,大鼠血浆中其药动学过程符合二室模型。主要药动学参数(拟合值):Cmax为3.96±0.51 mg·L-1,Tmax为16.31±2.85 min,t1/2β为5.16±0.77 h,CL为0.21±0.03 L·h-1·kg-1,AUC为7.91±1.02 mg·min-1·L-1,MRT为2.26±0.97 min。结论:本实验建立的血浆处理法及HPLC法适用于大鼠体内橙黄决明素的含量测定和药动学研究,灌胃给药后橙黄决明素吸收迅速,具有较好的应用前景。
OBJECTIVE: To establish a HPLC method for the determination of the content of the orange-yellow cassia seed in rat plasma and to study the pharmacokinetics of the orange-yellow-cassia seed in rats. Methods: The rats were orally administered with the dosage of 7.2 mg · kg-1 of Huanghuang Jiming Ming by gavage at 5,10,20,30 min and 1,2,3,4,6,8,10,12,16,24 h Plasma samples were processed by blood-liquid extraction and liquid-liquid extraction. HPLC was used to determine the concentration of the yellow-spot cassia seed in plasma. The pharmacokinetic parameters were fitted by 3P97 software. Results: The linear relationship between plasma concentration of cassia toxins in the range of 0.12 ~ 7.62μg · ml-1 was good with a correlation coefficient of 0.999 5 (n = 5). The extraction recoveries were> 95% at low, medium and high concentrations. All <10%, meet the requirements. After intragastric administration, the pharmacokinetics of rat plasma conformed to the two-compartment model. The main pharmacokinetic parameters (fitted values) were Cmax of 3.96 ± 0.51 mg · L-1, Tmax of 16.31 ± 2.85 min, t1 / 2β of 5.16 ± 0.77 h and CL of 0.21 ± 0.03 L · h-1 · kg -1, AUC was 7.91 ± 1.02 mg · min-1 · L-1 and MRT was 2.26 ± 0.97 min. Conclusion: The plasma treatment method and HPLC method established in this study are suitable for the determination of the content of Huang Huang cassia in rats and the study of pharmacokinetics. The absorption of Huang Huang Jinding Ming Su after oral administration has a good application prospect.