应用反相离子对色谱同时测定酸、碱及两性药物辛醇/水分配系数
Application of reversed-phase ion-pair chromatography for universal estimation of octanol-water partition coefficients of acid, basic and amphoteric drugs
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摘要:
建立一种适合同时测定酸、碱及两性药物辛醇/水分配系数 (log P) 的反相离子对色谱 (RP-IPC) 方法。基于有机相比例ф变化与相应的色谱保留参数log k' 值之间的线性关系, 回归计算相对于100 % 水相时分析物色谱保留log kw值, 并用于表征化合物log P值。测得各药物对照品log kw与文献报道“摇瓶法”测得log P值接近, 平均差值为0.31。三氟乙酸反相离子对色谱提高了测定适用范围, 且准确度较高, 可用于一定范围内酸碱度不同药物辛醇/水分配系数的同时测定。
Abstract:This paper is to establish a reversed-phase ion-pair chromatography (RP-IPC) method for universal estimation of the octanol/water partition coefficients (log P) of a wide range of structurally diverse compounds including acidic, basic, neutral and amphoteric species. The retention factors corresponding to 100% water (log kw) were derived from the linear part of the log k′/ф relationship, using at least four isocratic log k′ values containing different organic compositions. The log kw parameters obtained were close to the corresponding log P values obtained with the standard “shake flask” methods. The mean deviation for test drugs is 0.31. RP-IPC with trifluoroacetic acid as non classic ion-pair agents can be applicable to determine the log P values for a variety of drug-like molecules with increased accuracy.
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