Separation Science Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4bis, 9000, Ghent, Belgium.
Anal Bioanal Chem. 2013 Jul;405(18):6029-41. doi: 10.1007/s00216-013-7015-x. Epub 2013 May 30.
Several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier (BBB) into the central nervous system (CNS). In this article, the performance of a variety of micellar liquid chromatographic (MLC) methods and immobilized artificial membrane (IAM) liquid chromatographic approaches were compared for a set of 45 solutes. MLC measurements were performed on a C18 column with sodium dodecyl sulfate (SDS), polyoxyethylene (23) lauryl ether (Brij35), or sodium deoxycholate (SDC) as surfactant in the micellar mobile phase. IAM liquid chromatography measurements were performed with Dulbecco's phosphate-buffered saline (DPBS) and methanol as organic modifier in the mobile phase. The corresponding retention and computed descriptor data for each solute were used for construction of models to predict transport across the blood-brain barrier (log BB). All data were correlated with experimental log BB values and the relative performance of the models was studied. SDS-based models proved most suitable for prediction of log BB values, followed closely by a simplified IAM method, in which it could be observed that extrapolation of retention data to 0% modifier in the mobile phase was unnecessary.
已经有几种体外方法经过测试，以评估其预测药物穿透血脑屏障（BBB）进入中枢神经系统（CNS）的能力。在本文中，比较了多种胶束液相色谱（MLC）方法和固定化人工膜（IAM）液相色谱方法对 45 种溶质的性能。MLC 测量在 C18 柱上进行，胶束流动相中的表面活性剂为十二烷基硫酸钠（SDS）、聚氧乙烯（23）月桂醚（Brij35）或脱氧胆酸钠（SDC）。IAM 液相色谱测量使用 Dulbecco 的磷酸盐缓冲盐水（DPBS）和甲醇作为有机改性剂在流动相中。每个溶质的相应保留和计算描述符数据用于构建预测药物透过血脑屏障（log BB）的模型。所有数据均与实验 log BB 值相关联，并研究了模型的相对性能。基于 SDS 的模型被证明最适合预测 log BB 值，紧随其后的是简化的 IAM 方法，从中可以观察到，在流动相中向 0%改性剂外推保留数据是不必要的。
