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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(R2>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。
OBJECTIVE To establish the quantitative structure retention relationship of the drug in the bioassay of the micellar chromatography and to analyze the retention mechanism of the drug in the bioassay of the micellar chromatography and to predict the retention behavior of the new compound to guide the design of the new compound. Methods Linear regression of the retention factors of biodistribution of micelles and the basic physico-chemical parameters influencing drug absorption of 110 drugs were established by using stoichiometric methods such as stepwise regression and partial least-squares regression, and the prediction model of drug retention behavior was established. Results Based on the physico-chemical parameters that affect the absorption of drug, the quantitative structure retention of drug-micellar chromatography was established. External validation using the test set showed that the model has good predictive ability (R2> 0.82). The hydrophobicity of the drug [calculated value of logarithm of n-octanol / water partition coefficient (P), cal-culated logP, ClogP], charge (δ), molecular weight (MW), total surface area TSA) and so on its role in the biodistribution of micellar chromatography chromatographic significant. Conclusion The quantitative structure retention of drug in biodistribution of micellar chromatography is helpful to resolve the retention behavior of drugs, to guide the design of new compounds and to improve the success rate of new drug development.