Chiral Separation Techniques in Electrophoretic Analysis

Chiral separation by electrophoretic methods has become a cornerstone of modern analytical science, particularly in the pharmaceutical, agrochemical and food sectors. Capillary electrophoresis (CE) exploits differences in the mobility of enantiomers under an electric field, offering high resolution, minimal solvent consumption and rapid analysis times. The use of chiral selectors—most commonly cyclodextrin derivatives—enables transient diastereomeric interactions that produce distinct migration profiles for mirror‐image molecules. Method refinements include the application of dynamic capillary coatings to control electroosmotic flow and reverse enantiomer migration order, the integration of dual‐selector systems to enhance selectivity, and the coupling of CE to mass spectrometry for improved sensitivity and structural characterisation. Computational modelling and density functional theory have emerged as powerful allies to experimental optimisation, allowing prediction of binding energies and migration behaviour. Together, these developments underscore the global importance of electrophoretic chiral analysis in ensuring enantiomeric purity, guiding regulatory compliance and driving innovation in drug development and environmental monitoring.

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Recent work has introduced a capillary electrophoresis protocol for the antipsoriatic agent apremilast, screening multiple anionic cyclodextrin derivatives to achieve enantiomeric discrimination. Although initial resolution was insufficient, the strategic use of dynamic surface coatings allowed reversal of the enantiomer migration order and reliable determination of the minor enantiomer’s purity. A complementary study on the calcium channel blocker amlodipine combined experimental CE optimisation with semiempirical and density functional theory calculations. This synergistic approach identified carboxymethyl-β-cyclodextrin as an optimal selector, established conditions for baseline separation and elucidated the molecular origins of chiral recognition. A comprehensive review of capillary electromigration techniques has detailed the evolution of enantioselective methodologies, from electrokinetic chromatography employing novel pseudostationary phases to chiral capillary electrochromatography. It highlighted advances in hyphenated CE-MS interfaces, the promise of chiral ionic liquids, molecularly imprinted polymers and metal-organic frameworks as selectors, and the continued refinement of indirect detection and counter‐migration strategies.

Chiral Separation Techniques in Electrophoretic Analysis publication trend

The graph below shows the total number of articles in chiral separation techniques in electrophoretic analysis across all publications each year (not limited to Nature Index journals).

Technical terms

Capillary electrophoresis (CE): An electrokinetic separation technique using narrow capillaries and an applied voltage to resolve charged species.

Chiral selector: A molecule or supramolecular assembly added to the background electrolyte that forms transient complexes with enantiomers, enabling their separation.

Cyclodextrin: A cyclic oligosaccharide commonly used as a chiral selector owing to its hydrophobic cavity and multiple interaction sites.

Electroosmotic flow (EOF): Bulk movement of buffer solution in a capillary under an electric field, which influences analyte migration direction and speed.

Enantiomer migration order (EMO): The sequence in which two enantiomers elute under given electrophoretic conditions, which can be adjusted by selector and surface modifications.

Pseudostationary phase: A dispersed phase, such as micelles or supramolecular assemblies, introduced into the CE buffer to provide additional separation selectivity.

References

1. Chiral Separation of Apremilast by Capillary Electrophoresis Using Succinyl-β-Cyclodextrin—Reversal of Enantiomer Elution Order by Cationic Capillary Coating. Molecules (2023).
2. Chiral Recognition Mechanism of Amlodipine by Capillary Electrophoresis Using Carboxymethyl-β-cyclodextrin: An Experimental and Theoretical Study. ACS Omega (2025).
3. Past, present, and future developments in enantioselective analysis using capillary electromigration techniques. Electrophoresis (2020).