磷脂膜色谱用于评价药物与有序磷脂膜的相互作用磷脂膜色谱用于评价药物与有序磷脂膜的相互作用

目的使用磷脂膜色谱考察药物与有序磷脂膜的相互作用。方法使用磷脂膜色谱测定药物与有序磷脂膜的相互作用强度，表示为药物的膜亲和性参数(lg K_IAM)。使用正辛醇/水系统测定药物的疏水性参数(lg DO/W,7.4)。结果在有机调节剂百分比(φ) 0～30%范围内，容量因子对数值(lg K′_IAM)与φ呈现良好线性关系；对于3种有机调节剂(甲醇、乙醇和乙腈)，lg K′_IAM与φ间曲线截距相同，但斜率有显著差别。从对羟基苯甲酸甲酯到丁酯，每增加一个CH₂对测定的亲脂性参数差值(Δlg K_IAM和Δlg DO/W,7.4)具有相似的影响，但是从对羟基苯甲酸到甲酯的差值却明显偏离这个规律。结论磷脂膜色谱是一个简便、有效和快速的用于评价药物与有序磷脂膜相互作用的工具。

Evaluation of interaction between drugs and ordered phospholipid membrane by immobilized artificial membrane chromatography

AIM: To investigate the interaction between drugs and ordered phospholipid membrane using immobilized artificial membrane chromatography (IAMC). METHODS: IAMC was used to determine the interaction drugs with phospholipid membrane, expressed as membrane affinity (lg kIAM). An n-octanol/buffer system was also employed as the reference hydrophobicity (lg Do/w,7.4). RESULTS: Within the range of used acetonitrile percentages (phi) 0-30% in mobile phase, retention index (lg kIAM) showed excellent correlation with phi. Intercepts of fitted straight lines between lg kIAM and phi were comparable but slopes were much different for the three organic modifiers (acetonitrile, ethanol and methanol). Effects by adding CH2 substituent on lipophilicity difference (delta lg kIAM and delta lg Do/w,7.4) were similar for p-hydroxyl benzoic methyl ester to butyl ester, whereas different for p-hydroxylbenzoic acid to methyl ester. CONCLUSION: IAMC system is a convenient, efficient and rapid tool for determining membrane interaction.