新型GPR40激动剂ADD-16及其钠盐平衡溶解度和油水分配系数的研究  

Equilibrium solubility and oil-water partition coefficients of novel GPR40 agonist ADD-16 and its sodium salt

作　　者：马丽莎 林佳艳 李琦 郭凯蕾 何金穗 孙定康 王庆伟 刘雪英 MA Li-sha;LIN Jia-yan;LI Qi;GUO Kai-lei;HE Jin-sui;SUN Ding-kang;WANG Qing-wei;LIU Xue-ying(Department of Pharmacy,Air Force Medical University,Xi’an 710032;School of Life Sciences,Henan University,Kaifeng Henan 475004;Department of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046;Xi’an Qinhuang Hospital,Xi’an 710600)

机构地区：[1]空军军医大学药学系,西安710032 [2]河南大学生命科学学院,河南开封475004 [3]陕西中医药大学药学院,陕西咸阳712046 [4]西安秦皇医院,西安710600

出　　处：《中南药学》2024年第6期1582-1586,共5页Central South Pharmacy

基　　金：陕西省2021年创新能力支持计划(No.2021GCZX-07号);陕西省秦创原“科学家+工程师”队伍建设(No.2023KXJ-080号)。

摘　　要：目的测定ADD-16及其钠盐形式在不同溶剂中的平衡溶解度及油水分配系数,为其后续的体内研究及制剂开发提供依据。方法建立HPLC法定量测定ADD-16及其钠盐含量,考察ADD-16及其钠盐在不同有机溶剂和不同pH磷酸缓冲液中的平衡溶解度,测定ADD-16及其钠盐在正辛醇-水体系中的油水分配系数。结果ADD-16及其钠盐在醇类有机溶剂中的溶解度较高,尤其在极性较大的甲醇中溶解度最大,分别为8.87、333.03 mg·mL^(-1)。ADD-16及其钠盐在磷酸缓冲液中的溶解度随pH增加而增大,均在pH 7.4的缓冲液中溶解度最大,分别为6.63、796.86μg·mL^(-1)。ADD-16及其钠盐形式的油水分配系数分别为3.29、-0.45。结论ADD-16及其钠盐的溶解度均受溶剂极性及pH影响,ADD-16成盐后溶解度有显著提高,且油水分配系数明显下降,ADD-16钠盐可能有更好的成药性。Objective To determine the equilibrium solubility and oil-water partition coefficients of ADD-16 and its sodium salt in different solvents,providing a basis for its subsequent in vivo research and formula development.Methods HPLC was used to detect the equilibrium solubility of ADD-16 and its sodium salt in different organic solvents and phosphate buffer solutions with different pH values.The method was also used to detect the oil-water partition coefficients of ADD-16 and its sodium salt in the n-octanol water system.Results The solubility of ADD-16 and its sodium salt in alcohol was high,especially in methanol,with the highest solubility of 8.87 and 333.03 mg·mL^(-1),respectively.The solubility of ADD-16 and its sodium salt in phosphate buffer increased with pH,and both have the highest solubility(6.63 and 796.86μg·mL^(-1),respectively)in a pH 7.4 buffer.The oil-water distribution coefficients of ADD-16 and its sodium salt were 3.29 and-0.45,respectively.Conclusion The solubility of ADD-16 and its sodium salt is influenced by solvent polarity and pH value.After salt formation,the solubility of ADD-16 is obviously improved,and the oil-water distribution coefficient is decreased,indicating better drug formation performance of ADD-16 sodium salts.

关 键 词：GPR40 平衡溶解度 油水分配系数 高效液相色谱 

分 类 号：R943[医药卫生—药剂学]