An Investigation of Peak Shape Models in Chiral Separations

Abstract

The use of superficially porous particles in chromatography has led to significant improvements in separation efficiency. However, peak asymmetry in enantiomeric separations causes performance comparisons across particle types a challenge. In this study, we screened 28 pharmaceutically relevant compounds and developed practical methods to reduce peak asymmetry in normal phase chiral chromatography. The use of additives was found to be effective in reducing peak tailing for all compounds, including neutrals. Additionally, we observed that solvent mismatch with the eluent can cause system peak interference, which can be managed by reducing injection volumes. To more accurately assess the performance of the separations across the two column types, mathematical models that accounted for peak shape distortions were applied. After minimizing these distortions, we found that the SPP column had more efficient kinetics than the FPP column, despite the latter performing better in some separations. Our findings highlight the importance of optimizing peak shape in enantiomeric separations to achieve accurate and reliable results.