Characterization of biopartitioning micellar chromatography system using monolithic column by linear solvation energy relationship and application to predict blood-brain barrier penetration.
Characterization of biopartitioning micellar chromatography system using monolithic column by linear solvation energy relationship and application to predict blood-brain barrier penetration.
复制标题
通过线性溶剂化能关系对使用整体柱的生物分配胶束色谱系统进行表征，并应用于预测血脑屏障渗透。
DOI：
10.1016/j.chroma.2009.05.007
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Zhonggui He
中科院分区：
文献类型：
--
作者：
Rong Lu;Jin Sun;Yongjun Wang;Haiyan Li;Jianfang Liu;L. Fang;Zhonggui He
将线性溶剂化能关系(LSER)应用于整体柱生物分配胶束层析(BMC)体系的表征，并与其他物理化学和生物过程进行了比较。溶质体积和Hb碱度对溶质保留率的影响最大，溶质的偶极/极化率、Hb碱度、Hb酸度或过量的摩尔折射率都会降低溶质的保留率。LSER系数的主成分分析表明，该体系与药物生物膜转运过程具有一定的相似性，如血脑屏障穿透、经皮吸收和口服吸收。建立了药物透过血脑屏障的定量保留-活性关系(QRAR)，并评价了其对这一生物过程的预测能力。借助于高流速，整体柱在不改变BMC保留机理和不影响生物过程良好预测能力的情况下，极大地促进了大分子化合物的高通量分析。因此，BMC系统与整体柱一起，允许高通量地分析生物过程，如血脑屏障穿透。
The linear solvation energy relationship (LSER) was applied to characterize biopartitioning micellar chromatography (BMC) system using monolithic column, and was utilized to compare the above system with other physicochemical and biological processes in this study. The solute volume and HB basicity had the maximum influence on the retention of the solutes, and an increase in the dipolarity/polarizability, HB basicity, HB acidity or excess molar refraction of the solutes decreased the retention. Principal component analysis of LSER coefficients showed that the system had certain similarity to drug biomembrane transport processes, such as blood–brain barrier penetration, transdermal and oral absorption. The quantitative retention–activity relationship (QRAR) of drug penetration across blood–brain barrier was established and its predictive capability for this biological process was evaluated. With the aid of the high flow rate, the monolithic column significantly facilitated the high-throughput analysis of large compounds’ bank without changing the mechanism of the retention in BMC and without impairing good predictive capability of the biological processes. Accordingly, the BMC system, together with monolithic column, allows for high-throughput profiling the biological processes, such as blood–brain barrier penetration.