Effect of particle size on the speed and resolution of chiral separations using supercritical fluid chromatography

•Smaller particle columns were evaluated for fast chiral SFC separations.•Smaller 3 μm particles vs. 5 μm particles showed higher optimum linear velocity.•The van Deemter plots showed typical pattern observed in HPLC.•Use of 3 mL/min flow rate on the OD-3 column with 150 × 4.6 mm i.d. is recommended.

Fast chiral supercritical fluid chromatography (SFC) separations have become important due to the increasing use of high-throughput experimentation (HTE) in organic synthesis. These HTE experiments can generate hundreds of samples for chiral analysis that need to be assayed in a short time. In general, chiral SFC can provide much faster analysis times compared to liquid chromatography (LC). Additionally, columns packed with smaller particles can provide faster and more efficient separations. In this study, the effect of the particle size on the speed and resolution of chiral separations by SFC was evaluated. The performance of Chiralcel OD columns packed with either 5 or 3 μm particles were compared using van Deemter or other kinetic plots. The benefits of using smaller particle columns for chiral SFC analysis are illustrated.