Evaluation and Implementation of a Commercially Available Mass-Guided SFC Purification Platform in a High Throughput Purification Laboratory in Drug Discovery

Abstract

The evaluation and implementation of a commercially available, off the shelf, analytical SFC/MS and a mass directed, semi-preparative SFC-MS system for use in a high throughput purification laboratory is described. The advantages of the use of SFC to support high throughput purification includes rapid evaporation of the chromatographic mobile phase in isolated fractions, resulting in faster sample turnaround time. In addition, SFC provides a complimentary separation technique based on normal phase, adsorption chromatography mechanisms. The screening scheme employed on the associated analytical SFC-MS and the methodology developed for the mass directed, semi-prep SFC-MS are presented in detail. The utilization of standard FractionLynx/AutoPurify functionalities to enable rapid incorporation into high throughput environments is also emphasized.

Keywords:

• Drug discovery
• High throughput
• Mass guided SFC
• Preparative SFC
• Purification
• SFC-MS

ACKNOWLEDGMENTS

The authors would like to thank THAR, Waters, Bill Wranitz, Matt Przybyciel, Denise Heyburn, Chuck Ross, and Vince Van Nostrand for their assistance in achieving SFC capabilities.