蟾酥提取物中2种蟾蜍甾烯类成分兔体内药代动力学研究

目的:建立兔血浆中2种蟾蜍甾烯类化合物蟾毒灵及酯蟾毒配基的分析方法,探讨其在兔体内的药代动力学过程。方法:兔按0.35 mg.kg-1由耳缘静脉注射蟾酥提取物后分别于2,5,10,15,20,30,45,60,90 min心脏取血,采用乙腈沉蛋白与液液萃取相结合方法进行血浆样品预处理,以HPLC测定兔血浆中蟾毒灵及酯蟾毒配基的浓度,以Kinetica软件拟合药动学参数。结果:建立的HPLC方法,蟾毒灵、酯蟾毒配基均得到很好的分离,达到体内分析要求。经非房室模型拟合,得到了蟾毒灵、酯蟾毒配基在兔体内主要药动学参数。结论:建立的蟾毒灵、酯蟾毒配基血药浓度测定方法及所获得的药动学参数,可为中药蟾酥提取物的药代动力学研究提供参考。

Studies on Simultaneous Determination and Pharmacokinetics of Two Bufadienolides in Rabbits Plasma

Objective: To establish a HPLC method for the assay of bufalin (BL), resibufogenin (RBG) and study the pharmacokinetics of BL, RBG in rabbits plasma. Method: The sample blood from rabbits were injected venenum bufonis extract by 0.35 mg·kg^-1 at 2,5,10,15,20,30,45,60,90 min. Protein precipitation with acetonitrile and liquid-liquid extraction was applied to purify plasma samples and used HPLC to determine the concentration of BL, RBG in it. The pharmacokinetics parameters were accessed by Kinetica software. Result: In this HPLC method, the separation, precision and accuracy of BL, RBG were well. The calibration curves were linear. The analytical recoveries were all more than 90%, intra and inter-day precision RSD were all less than 15.0% ( n =5). The main pharmacokinetics parameters were fitted by non-compartment models. Conclusion: The HPLC method can be used to determine the concentration and to investigate the pharmacokinetics of BL and RBG.