Evaluation of flash supercritical fluid chromatography and alternate sample loading techniques for pharmaceutical medicinal chemistry purifications

Flash chromatography is the preferred approach for small molecule purification in pharmaceutical discovery. This paper will discuss the potential for flash supercritical fluid chromatography (SFC) as an alternative technology for these purifications. It was shown that the high sample loadings seen with flash LC could also be achieved using flash SFC. The dry load injection technique greatly increases the amount of sample that can be applied to a flash SFC column while still achieving separation. Flash SFC has much lower solvent usage and higher purification productivities relative to flash LC. Product concentrations post purification were higher for flash SFC vs. flash LC, reducing the time required to isolate dry product. There still exist a number of technical details to be worked out with flash SFC, mainly around the equipment and column/cartridge technology.

► High sample loadings were achieved using dry pack technique with flash SFC. ► Flash SFC had comparable loadings with lower solvent consumption relative to flash LC. ► Products from flash SFC were approximately four times more concentrated than flash LC. ► Use of flash SFC may reduce dichloromethane use.