Chiral Capillary Electrokinetic Chromatography: Principle and Applications, Detection and Identification, Design of Experiment, and Exploration of Chiral Recognition Using Molecular Modeling

Abstract

This work reviews the literature of chiral capillary electrokinetic chromatography from January 2016 to March 2021. This is done to explore the state-of-the-art approach and recent developments carried out in this field. The separation principle of the technique is described and supported with simple graphical illustrations, showing migration under normal and reversed polarity modes of the separation voltage. The most relevant applications of the technique for enantioseparation of drugs and other enantiomeric molecules in different fields using chiral selectors in single, dual, or multiple systems are highlighted. Measures to improve the detection sensitivity of chiral capillary electrokinetic chromatography with UV detector are discussed, and the alternative aspects are explored, besides special emphases to hyphenation compatibility to mass spectrometry. Partial filling and counter migration techniques are described. Indirect identification of the separated enantiomers and the determination of enantiomeric migration order are mentioned. The application of Quality by Design principles to facilitate method development, optimization, and validation is presented. The elucidation and explanation of chiral recognition in molecular bases are discussed with special focus on the role of molecular modeling.

Recent developments in capillary and microchip electroseparations of peptides (2019–mid 2021)

“…For this reason, the chiral analysis of peptides and separation of their stereoisomers, especially in the case of peptide pharmaceuticals, is extremely important. Thanks to their high separation efficiency and resolution power, short analysis times, and low sample and selectors, and other chemicals consumption, CE methods are very powerful methods for chiral analysis and separation of stereoisomers in general [264][265][266][267], including chiral and stereoselective separations of peptides, as shown recently [268] or earlier [269,270].…”

Capillary Electrophoresis Mass Spectrometry: Developments and Applications for Enantioselective Analysis from 2011–2020

“…Apart from the aforementioned enantioselective interactions, the solute's adsorption to the column walls must be considered to understand the analyte retention behavior. For more recent details on the enantioselective mechanisms in CE, several excellent reviews are available [10,11].…”

Immunoaffinity Capillary Electrophoresis in the Era of Proteoforms, Liquid Biopsy and Preventive Medicine: A Potential Impact in the Diagnosis and Monitoring of Disease Progression

“…The basic principle of capillary electrophoresis is the separation of ions based on their electrophoretic mobility (mass/charge ratio) with the use of an applied voltage. Capillary electrophoresis can separate a wide range of chemical and biochemical entities, including neutral substances, cellular and subcellular entities, and nanoparticles or nanovesicles using one or more of 9 different separation modes [144][145][146][147][148][149][150][151]. Because of this, CE is known for its high-power resolution, high sensitivity and rapidity, high peak capacity, high separation efficiency with reproducible quantification, the use of small sample volumes with low waste generation, on-column and off-column detection, automation, low cost of operation, use of miniaturized components, option of multiple detection systems, and a diverse range of applications [144][145][146][147][148][149][150][151].…”

“…Furthermore, using narrow capillaries helps to reduce band-broadening seen in the peaks generated in other techniques such as high-performance liquid chromatography (HPLC). As a result, separation efficiency in CE is very high [144][145][146][147][148][149][150][151]. As opposed to conventional electrophoresis, which is labor-intensive and can take several hours to perform, CE can be completely automated and only a few microliters of sample are needed for an analysis to be carried out in a few minutes [123,151].…”