Evaluation of injection conditions for preparative supercritical fluid chromatography

Preparative supercritical fluid chromatography (SFC) has become the preferred method for the rapid purification of drug candidates during the pharmaceutical discovery process. This paper will discuss the evaluation of injection techniques for preparative SFC. A thorough evaluation of mixed stream vs. modifier stream™ injection was performed. It was shown that for the majority of the compounds evaluated, modifier stream injection gave better resolution relative to mixed stream injection. The improvement in resolution with modifier stream injection increased as injection volume increased. In addition, a study evaluating the effect of dissolution solvent on chromatographic performance for the preparative resolution of enantiomers using SFC showed that dissolution solvent had minimal impact on preparative resolution for the preparative SFC separation of trans stilbene oxide.

► Two injection techniques were evaluated for preparative SFC purifications.
► For the majority of the compounds modifier stream injection gave better resolution.
► Resolution improvement with modifier stream injection increased with injection volume.
► Dissolution solvent has minimal impact on preparative SFC resolution of TSO.