The importance of the stereochemistry of pharmaceutical drugs is well recognized because stereoisomers often differ in their pharmacological, toxicological and/or pharmacokinetic profiles. As a consequence, the majority of small molecule drugs of the top 10 products according to their worldwide sales in 2023 are single enantiomer drugs [1]. For drug development and quality control, the determination of the stereoisomeric composition and purity of a compound requires sensitive and accurate analytical methods in order to determine the stereoisomer ratios in synthetic products, pharmaceutical formulations and biological samples. Besides HPLC, CE has become an attractive alternative for this purpose.

In CE, the chiral selector is added to the background electrolyte acting as a pseudostationary phase, which is also mobile in contrast to chromatographic methods. Consequently, two stereoselective principles contribute to stereoisomer separations, i.e. the formation of transient diastereomeric complexes between analyte enantiomers and the chiral selector (also referred to as the thermodynamic or chromatographic enantioselective mechanism) as well as the mobility of these complexes (electrophoretic enantioselective mechanism). Both principles can cooperate or counteract each other.

The current presentation will discuss recent applications of chiral CE methods for the determination of the enantiomeric purity of pharmaceutical drugs such as silodosin, tamsulosin, tenofovir or dextromethorphan. The methods were developed using a quality by design (QbD) approach and design of experiment (DoE) methodologies and eventually applied to the analysis of bulk drug or pharmaceutical formulations.

[1] N.A. McGrath, M. Brichacek, J.T. Njardarson, A Graphical Journey of Innovative Organic Architectures That Have Improved Our Lives, J. Chem. Ed. 87 (2010) 1348-1349; https://sites.arizona.edu/njardarson-lab/top200-posters, Top 200 Small Molecule Drugs by Sales in 2024 Poster.