Separation of achiral analytes using supercritical fluid chromatography with chiral stationary phases

• Solving multicomponent achiral separation challenges via SFC with chiral stationary phases (CSPs).
• Challenging mixtures of achiral drug metabolites and analogs can often be resolved by CSPs in SFC mode.
• Achiral UHPLC and SFC vs chiral SFC for separation of closely related achiral analytes.
• Separation of complex non-enantiomeric mixtures often require alternative approaches such as chiral SFC.

In recent years, chiral supercritical fluid chromatography (SFC) has emerged as the preferred technique for analytical, semi-preparative and preparative separation of enantiomers in the pharmaceutical industry, due to advantages in speed, high column efficiency and significantly lower mobile-phase consumption than conventional liquid chromatography (LC) techniques. We illustrate the benefits of SFC using chiral stationary phases (CSPs) in method development for separating multicomponent mixtures of closely-related achiral analytes, including hydroxylation isomers, halogen-containing molecules, drug metabolites and analogs, methylation and demethylation species, constitutional isomers, and diastereomers. We present several case studies to illustrate the advantage of using SFC with CSPs for achiral separations, where conventional achiral LC and achiral SFC methods fail or deliver sub-optimal chromatographic performance.