Chiral analysis of poor UV absorbing pharmaceuticals by supercritical fluid chromatography-charged aerosol detection

•SFC-CAD for chiral analysis of organic compounds with weak UV absorption.•Accurate measurement of the enantiopurity by SFC-CAD compared to SFC-UV.•SFC-UV-CAD as a chromatographic screening system for method development.•High-throughput chiral analysis of reaction mixtures without the need of sample derivatization.

Fast and efficient chiral analysis of drugs and synthetic intermediates with weak UV absorption is one of the most challenging analytical tasks in modern pharmaceutical research and development. In this study, the use of supercritical fluid chromatography-charged aerosol detection (SFC-CAD) for chiral analysis of poor UV absorbing analytes commonly encountered during pharmaceutical process research was investigated. Investigation of makeup flow rate showed that CAD responses remained largely steady from 1 to 1.5 mL/min for different mobile phase compositions. The effect of the additives in the mobile phase and the makeup flow on the background noise of CAD detection was also studied. Accurate measurement of the enantiopurity of pharmaceuticals from −100% to 100% enantiomeric excess (ee) was achieved under isocratic conditions. The SFC-CAD system was used as a chromatographic screening system for method development and successfully applied to high-throughput chiral analysis of reaction mixtures in microtiter plates.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide