非布索坦平衡溶解度、表观油水分配系数及解离常数的测定  

Determination of equilibrium solubility,apparent oil/water partition coefficient and dissociation constant of febuxostat

作　　者：张琪[1] 龚耘[1] 劳嘉泳[1] 张怡[1] 刘中秋[1] 蔡铮[1] 

机构地区：[1]南方医科大学药学院,广州510515

出　　处：《中国新药杂志》2013年第1期103-106,共4页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30902009)

摘　　要：目的:测定非布索坦的平衡溶解度、表观油水分配系数及解离常数。方法:采用超高效液相色谱法测定非布索坦在37℃下不同pH值缓冲液中的平衡溶解度及表观油水分配系数,并分别通过平衡溶解度法及紫外吸光度法测定其解离常数。结果:非布索坦的平衡溶解度随缓冲液的pH值升高而增大,而表观油水分配系数则相应减小,当pH为7.0时,平衡溶解度为246.4 mg.L-1,表观油水分配系数为15.49;平衡溶解度法与紫外吸光度法测得的非布索坦的解离常数十分接近,分别为4.08与4.07。结论:非布索坦的溶解度较小,在酸性条件下几乎不溶,中性条件下极微溶解,碱性条件下微溶,不适合制备静注制剂,但由于其油水分配系数较高,具有较强的跨膜能力,可采用口服途径给药。Objective： To determine equilibrium solubility（Cs）,apparent oil/water partition coefficients（Papp） and dissociation constant（pKa） of febuxostat.Methods： Ultra performance liquid chromatography method was established to measure equilibrium solubility and logPapp of febuxostat at 37 ℃ in buffer solutions with various pH values.The pKa was determined by equilibrium solubility method and UV spectrophotometry,respectively.Results： With the rise of pH value,the Cs of febuxostat increased correspondingly,and apparent oil/water partition coefficients decreased inversely.When the pH value was 7.0,Cs was 246.4 mg·L-1 and logPapp was 1.19.The pKa values measured by equilibrium solubility method and UV spectrophotometry were 4.08 and 4.07,respectively.Conclusion： Febuxostat is insoluble in acidic condition,very slight soluble in neutral condition,and slight soluble in alkaline condition;thus,it is unsuitable for intravenous injection because of the poor water solubility.However,oral administration is recommended due to its proper lipophilicity and high permeability.

关 键 词：非布索坦 平衡溶解度 表观油水分配系数 解离常数 

分 类 号：R913[医药卫生—药学]