蟾毒灵白蛋白纳米粒与蟾毒灵在大鼠体内的药代动力学比较研究  

A comparison study of pharmacokinetics between bufalin-loaded bovine serum albumin nanoparticles and bufalin in rats

作　　者：张慧卿[1,2] 殷子斐[2] 盛佳钰[1,2] 姜珠倩[1,2] 吴宝玉[1,2] 苏永华[2] 

机构地区：[1]上海中医药大学中药研究所,上海201203 [2]第二军医大学长海医院中医系,上海200433

出　　处：《中西医结合学报》2012年第6期674-680,共7页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金重大国际合作项目 (No30810103910);国家自然科学基金面上项目(No30901986)

摘　　要：目的:建立高效液相-串联质谱法测定大鼠血浆中蟾毒灵的浓度,评价和比较蟾毒灵白蛋白纳米粒和蟾毒灵在大鼠体内的药代动力学特征。方法:30只大鼠随机分为6组,每组5只,尾静脉单次分别注射蟾毒灵纳米粒和蟾毒灵,均设高、中、低剂量组。分别于给药后1、5、8、10、15、20、30、45、60、120、180、300和480min从大鼠眼眶静脉丛取血,高效液相-串联质谱法测定不同时间点血浆中药物浓度,并测定药代动力学参数。结果:本实验所建立的高效液相-串联质谱法具有良好的线性、精密度和准确度。蟾毒灵纳米粒组的血浆药-时曲线下面积和平均滞留时间、半衰期分别是蟾毒灵组的1.19～1.81倍、2.12～3.61倍和2.17～2.94倍。结论:蟾毒灵白蛋白纳米粒可延长蟾毒灵在血中的存留时间,具有缓释作用。OBJECTIVE： To determine the bufalin concentration in rats’ plasma by establishing a high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method, and to evaluate and compare the pharmacokinetic characteristics of bufalin-loaded bovine serum albumin nanoparticles （bufalin-BSA-NP） and bufalin. METHODS： Thirty Wistar rats were randomly divided into six groups with five rats in each group, and administered with a single dose of 0.6, 0.3 and 0.15 mg/kg of bufalin-BSA-NP or bufalin, respectively. After the administration, blood samples were collected from the orbital venous plexus at designed time points （1, 5, 8, 10, 15, 20, 30, 45, 60, 120, 180, 300 and 480 min）. The concentration of bufalin in plasma at different sampling time points was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and compared. RESULTS： The established HPLC-MS/MS method had high linearity, precision and accuracy. The blood plasma area under curve, the mean retention time and the terminal half life of bufalin-BSA-NP were 1.19 to 1.81, 2.12 to 3.61 and 2.17 to 2.94 times of bufalin, respectively. CONCLUSION： Bufalin-BSA-NP has the function of sustained release thus to prolong the bufalin remaining in blood.

关 键 词：蟾毒灵 纳米粒子 药代动力学 色谱法 高压液相 串联质谱法 大鼠 

分 类 号：R285.5[医药卫生—中药学]