高效液相色谱法测定去氧氟尿苷在不同介质中的平衡溶解度和表观油水分配系数

目的测定去氧氟尿苷在不同介质中的平衡溶解度以及在正辛醇-水和正辛醇-缓冲液体系中的表观油水分配系数。方法采用HPLC法测定去氧氟尿苷的浓度,采用摇瓶法测定去氧氟尿苷的表观油水分配系数。结果37℃,pH=7时去氧氟尿苷在水中的平衡溶解度为2.570 1 g.L-1,在pH〈5磷酸盐缓冲液中的平衡溶解度较低;去氧氟尿苷在正辛醇和水相中表观油水分配系数Papp为0.97;当pH〈7时,受pH影响不显著,表现为亲水性。结论去氧氟尿苷在水中的平衡溶解度及油水分配系数与介质的pH值有关,可以通过改变pH值,增加该药物新剂型的稳定性。

Determination of equilibrium solubility of doxifluridine in various media and its apparent oil/water partition coefficient by HPLC

Objective To determine the equilibrium solubility of doxifluridine in various media and its apparent partition coefficient for the n-octanol-water/buffer solution system.Methods A high performance liquid chromatography was established and used to detect the concentration of doxifluridine.The apparent partition coefficient for the n-octanol-water/buffer solution system of doxifluridine was determined by shaking flask method.Results The equilibrium solubility of doxifluridine in water was 2.570 1 g·L-1 at 37 ℃ and had lower values in acidic phosphate buffer solution.Papp of doxifluridine was 0.97.It was hydrophilic when pH7,and had no significant effect.Conclusion The equilibrium solubility and apparent partition coefficients of doxifluridine are correlated to pH of the medium.The stability of new dosage form of drugs can be increased by changing pH value.