Roman Szucs

On-line two-dimensional liquid chromatography (2D-LC) embracing mainly comprehensive LC (LC×LC) and multiple heart-cutting LC (mLC–LC) offers new opportunities for in-depth characterization of pharmaceuticals. Reversed-phase LC × reversed-phase LC using different column chemistries and mobile phases provides good orthogonality for a wide range of applications related to small molecule drugs. Moreover, hardware configurations and software are now commercially available to perform LC×LC and mLC–LC measurements in a reproducible manner.

The principal aim of this work was to provide a perspective with practical utility in streamlining the chromatographic method development in pharmaceutical industries based upon predicting the chromatographic retention times from molecular structures. Workflows were suggested with a focus on reversed-phase LC, IC, and HILIC as the three major techniques. Unlike HILIC, retention prediction in both reversed-phase LC and IC can benefit from the maturity of these techniques and the transparency of their retention mechanisms. In reversed-phase LC the solute coefficients in the hydrophobic subtraction model and in IC the a and b values in the linear solvent strength model can be the subject of modelling with their subsequent use in retention prediction. A workflow for HILIC can be based on the design of experiments approach, to account for all major contributors to the retention mechanism, and direct correlation of experimental retention times to the molecular descriptors.