Supercritical Fluid Chromatography for Chiral Analysis, Part 1: Theoretical Background

Abstract

The quantification of the enantiomers of racemic substances is of great importance in the development and regulation of pharmaceutical compounds. Active ingredients are often chiral; typically, only one of the stereoisomers has the desired pharmacokinetic and/or pharmacodynamic properties. Therefore, the stereoisomer distribution of chiral drug products must be characterized and evaluated during the drug discovery and development pipeline. Moreover, various chiral drugs present a stereoselective metabolism, highlighting the need for appropriate analytical strategies for the stereoselective analysis of metabolites, for example, in clinical and environmental studies. Due to its ease of use, robustness, and transferability, chiral liquid chromatography (LC) is the most common approach used in pharmaceutical analysis. Compared with LC, supercritical fluid chromatography (SFC) allows higher linear flow velocities while maintaining high chromatographic efficiency, often enabling the reduction of analysis time. In addition, SFC provides enhanced or complementary chiral selectivity and avoids or reduces toxic solvents, such as those used in normal-phase LC. In the first part of this review article the theoretical advantages, technological developments, and common practices in chiral SFC are discussed. This will be followed by a contribution discussing recent applications in pharmaceutical, clinical, forensic, and environmental analysis.