中文摘要：

目的建立药物在生物分配胶束色谱的定量结构保留关系,解析药物在生物分配胶束色谱的保留机理,用于预测新化合物的保留行为,以指导新化合物的设计。方法采用逐步回归与偏最小二乘回归等化学计量学方法,对110个药物的生物分配胶束色谱保留因子与影响药物吸收的基本物理化学参数等进行线性回归,建立药物保留行为的预测模型。结果建立了基于影响药物吸收的物理化学参数的药物生物分配胶束色谱定量结构保留关系,采用测试集进行外部验证显示模型具有良好的预测能力（R^2〉0.82）。药物的疏水性[正辛醇/水分配系数（P）的对数值的计算值,cal-culated logP,ClogP]、电荷（δ）、分子量（molecular weight,MW）、总表面积（total surface area,TSA）等对其在生物分配胶束色谱的色谱保留作用显著。结论药物在生物分配胶束色谱的定量结构保留关系建立有助于解析药物的保留行为,指导新化合物的设计,提高新药研发的成功率。

英文摘要：

Objective To establish quantitative structure retention relationship for structure diverse drugs with biopartitioning micellar chromatography,elucidate the retention mechanism and predict the retention behavior,which is benefiting for the design of new chemical entities.Methods Chemometrics methods,stepwise regression and partial least squares regression were utilized to establish quantitative structure retention relationship for 110 structure diverse drugs based on basic physicochemical molecular descriptors（ClogP,rings,rotation bonds,et al）which affecting the drug absorption processes.Results The obtained models exhibited good predictability（R^2〉0.82）.The hydrophobicity（Clog P）,the mean net charge per molecule（δ）,the molecular weight（MW）and the total surface area（TSA）were the main factors influenced the retention behavior of the drugs in biopartitioning micellar chromatography.The hydrophobicity（Clog P）had the most significant positive effect;however,the mean net charge per molecule（δ）had significant negative effect.The power of prediction of the above model was evaluated and validated using an external test set,and as a result,the presented model had satisfying predictive ability.Conclusions The establishment of quantitative structure retention relationship for compounds with biopartitioning micellar chromatography contributes the design of new chemical entities;improves the efficiency of research and development of new drugs.