An Orthogonal Approach to Chiral Method Development Screening

Abstract

Many of the new chemical entities under development in the pharmaceutical industry are chiral. The specific stereochemistry of these substances affects both the biological activity and commercial viability of the potential new drug. Thus, enantioselective separation techniques play a vital role in the development of these entities into commercial products. In an attempt to improve upon the efficiency of chiral method development, column manufacturers and industry scientists have developed screening procedures to efficiently evaluate various chiral separation conditions in an unattended mode. While these systems have been shown to be successful in their initial and literature studies, it is important to evaluate these systems for the molecules of interest to each particular business concern. After optimizing the analysis conditions of several literature chiral screening procedures, the individual screens were challenged by novel chemical entities developed for commercial use. The entities were randomly selected based on availability and how well they represent molecules of interest to common pharmaceutical portfolios. Our chiral screening program is currently focusing on four separation technologies: a) Liquid Chromatography (LC), b) Supercritical Fluid Chromatography (SFC), c) Capillary Electrophoresis (CE), and Gas Chromatography (GC). An overview of the results from each of these screens, future directions and a final unified strategy for chiral method development screening are presented. Keywords: Chiral screening, Liquid chromatography, Supercritical fluid chromatography, Capillary electrophoresis