去氢骆驼蓬碱衍生物H-Y-B在不同介质中平衡溶解度、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 a dehydrocamarine derivative H-Y-B in different media

作　　者：王鑫 高惠静[2] 徐楠 王建华[2] 滕亮[2] WANG Xin;GAO Hui-jing;XU Nan;WANG Jian-hua;TENG Liang(College of Pharmaceutical Sciences,Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;Department of Pharmacy,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学药学院,新疆维吾尔自治区乌鲁木齐830011 [2]新疆医科大学第一附属医院药学部,新疆维吾尔自治区乌鲁木齐830054

出　　处：《中国临床药理学杂志》2023年第5期742-746,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区自然科学基金资助项目(2020D01C245)。

摘　　要：目的测定去氢骆驼蓬碱衍生物H-Y-B在不同pH缓冲液及不同溶剂中的平衡溶解度、正辛醇-水/缓冲溶液体系中的表观油水分配系数(lgP)及其解离常数(pKa),为H-Y-B的剂型设计提供依据。方法采用HPLC法测定H-Y-B的浓度,以饱和溶液法测定H-Y-B在不同pH缓冲液及不同溶剂中的平衡溶解度;以正辛醇-水/缓冲溶液为模拟系统,采用摇瓶法-HPLC法测定H-Y-B的表观油水分配系数;使用紫外分光光度法测定H-Y-B的解离常数。结果在37℃下,H-Y-B在pH为10.3中的溶解度最高,为(418.62±1.68)mg·mL^(-1),在pH为1.83中的溶解度最低,为(189.21±1.58)mg·mL^(-1)。H-Y-B在水中的溶解度为(305.82±2.43)mg·mL^(-1),在有机溶剂中的溶解度顺序为甲醇>二甲基亚砜>乙醇>异丙醇>正辛醇>乙腈>丙酮>乙酸乙酯;H-Y-B在水中lgP为0.63,在pH 6.8缓冲液中的lgP为0.50;H-Y-B的pKa值为(6.42±0.52)。结论H-Y-B为强极性化合物,脂溶性较差,推测药物不易透过细胞膜吸收和转运,且pH能影响表观油水分配系数,本研究可为H-Y-B口服吸收研究及新剂型设计提供依据。Objective To determine the equilibrium solubility,apparent oil-water partition coefficient(lgP)and dissociation constant(pKa)of the n-octanol-water/buffer solution in different pH buffers and solvents,and to provide basis for the formulation design of H-Y-B.Methods The concentration of H-Y-B was determined by HPLC,and the equilibrium solubility of H-Y-B in different pH buffers and different solvents was determined by saturated solution method.Using n-octanol-water/buffer solution as the simulation system,the apparent oil-water partition coefficient of H-Y-B was determined by shaking flask method and HPLC method.The dissociation constant of H-Y-B was determined by ultraviolet spectrophotometry.Results At 37℃,the solubility of H-Y-B was the highest(418.62±1.68)mg·mL^(-1)in pH 10.3,and the lowest(189.21±1.58)mg·mL^(-1)in pH 1.83.The solubility of H-Y-B in water was(305.82±2.43)mg·mL^(-1),and the order of solubility in organic solvents is methanol>dimethyl sulfoxide>ethanol>isopropanol>n-octanol>acetonitrile>acetone>ethyl acetate.The lgP of H-Y-B was 0.63 in water and 0.50 in pH 6.8 buffer.The pK a value of H-Y-B was(6.42±0.52).Conclusion H-Y-B is a strong polar compound with poor lipid solubility,so it is speculated that the drug is not easy to be absorbed and transported through cell membrane,and p H can affect the apparent oil-water partition coefficient.This study can provide basis for the study of oral absorption of H-Y-B and the design of new dosage forms.

关 键 词：去氢骆驼蓬碱衍生物H-Y-B 平衡溶解度 表观油水分配系数 解离常数 高效液相色谱法 

分 类 号：R28[医药卫生—中药学]