巴戟甲素表观油水分配系数和血清蛋白结合率的测定

Determination of the apparent oil-water partition coefficient and serum protein binding rate of Bajijiasu

目的测定巴戟甲素的表观油水分配系数和血清蛋白结合率,为该化合物体内药动学研究提供依据。方法应用HPLC-ELSD检测仪,采用摇瓶法测定巴戟甲素表观油水分配系数,超滤法测定其血清蛋白结合率。结果巴戟甲素在正辛醇-水(体积比1:1、2:1)中的表观油水分配系数均值为0.052 5(logρapp=-1.28),在正辛醇-磷酸盐缓冲液(pH6.8,体积比1:1、2:1)中均值为0.0507(logρapp=-1.295)。测定的巴戟甲素与牛血清白蛋白(BSA)、人血清白蛋白(HSA)和大鼠血清蛋白结合率分别为42.15%、40.67%、30.89%。结论巴戟甲素水溶性较强,在正辛醇-水中的表观油水分配系数与在正辛醇-磷酸盐缓冲液中基本一致;与BSA、HSA结合率高于其与大鼠血清蛋白的结合率,提示巴戟甲素可能主要与血清中的白蛋白产生特异性结合。

Objective To determine the apparent oil-water partition coefficient and serum protein binding rate of Bajijiasu which might support for its pharmaeokinetics research in vivo. Methods HPLC-ELSD was used for the assay of Bajijiasu, and the partition coefficients were determined by shaking flask method. The ultrafiltration method was employed to obtain the serum protein binding rates. Results The apparent oilwater partition coefficient in octanol/water system was 0. 052 5 （ logpapp = - 1.28 ） and 0. 050 7 （ logpapp = - 1. 295 ） in octanol/phosphate buffer （ pH = 6.8 ） system. The serum protein binding rates of Bajijiasu with BSA, HSA and rat serum protein were 42. 15%, 40. 67%, 30. 89% , respectively. Conclusion Bajijiasu was a hydrotropie substance. The partition coefficients in octanol/water system is identical with oetanol/phosphate buffer （pH = 6.8 ） system. The serum protein binding rate of Bajijiasu with BSA,HAS was significantly higher than other rat serum protein, which showed that Bajijiasu may have a kind of specific binding with albumin in serum.