Retention Time Prediction Based on Molecular Structure in Pharmaceutical Method Development: A Perspective

Abstract

The principal aim of this work was to provide a perspective with practical utilityin streamlining the chromatographic method development in pharmaceuticalindustries based upon predicting the chromatographic retention times frommolecular structures. Workflows were suggested with a focus on reversedphaseliquid chromatography (LC), ion chromatography (IC), and hydrophilicinteractionchromatography (HILIC) as the three major techniques. UnlikeHILIC, retention prediction in both reversed-phase LC and IC can benefit fromthe maturity of these techniques and the transparency of their retentionmechanisms. In reversed-phase LC the solute coefficients in the hydrophobicsubtraction model and in IC the a and b values in the linear solvent strengthmodel can be the subject of modeling with their subsequent use in retentionprediction. A workflow for HILIC can be based on the design of experimentsapproach, to account for all major contributors to the retention mechanism, anddirect correlation of experimental retention times to the molecular descriptors.