Chemometric analysis of bio-inspired micellar electrokinetic chromatographic systems – modelling of retention mechanism and prediction of biological properties using bile salts surfactants

Abstract The development of screening methods for the estimation of physicochemical, biological and pharmacokinetic properties of new pharmaceutical agents at early stage of the drug discovery and development process is highly desirable. Due to inadequate properties many of drug candidates are rejected during clinical trials. Among available screening methods, both chromatographic and electrophoretic approaches have a well-established position. This work is continuation of our research focused on developing new micellar electro-kinetic chromatographic methods for rapid assessment of complex biological properties. In this work an extended set of 45 compounds was used in order to realize two main goals. The first one was the characterization of molecular mechanism of retention in sodium cholate and sodium deoxycholate MEKC systems using quantitative structure-retention relationships (QSRR) approach. The second goal was evaluation of the possibilities to use MEKC with sodium cholate and sodium deoxycholate pseudo-stationary phases in order to predict human intestinal absorption (HIA). The proposed quantitative retention-activity relationships (QRAR) model was additionally supported by theoretical descriptors and support vector machine (SVM) regression. Additionally, the prediction ability of obtained QRAR models were compared with PREADME software. The obtained results suggest that SVM model has better predictive abilities and is better suited to separate noise which accompanies the experimental and computational descriptors.