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.
Highlights
Chirality plays a crucial role in life with a multidisciplinary interest—including, but not limited to, chemistry, biochemistry, food chemistry, agrochemistry, drug discovery, pharmacology, engineering, physics, and material science
Some examples showed an enhanced separation efficiency through dual CS systems Recently, La et al [86] developed a capillary electrokinetic chromatography (CEKC) method based on a multiple chiral separain which the two chiral selectors are introduced to the capillary in two separated plugs
Important than theconcentration absolute concentration. It is worth noting playsrole an in this regard, and an impurity enantiomer peak eluted before the peak of the main enantioimportant role in this regard, and an impurity enantiomer peak eluted before the peak of mer is lessenantiomer likely to overlap with the possible tailing of the main enantiomeric peak
Summary
Chirality plays a crucial role in life with a multidisciplinary interest—including, but not limited to, chemistry, biochemistry, food chemistry, agrochemistry, drug discovery, pharmacology, engineering, physics, and material science. Regulations to quantify enantiomeric impurity of 0.1% relative to the main enantiomer This has been established in the guidelines of ICH and the other regulatory authorities, such as the Food and Drug Administration (FDA) and European Medical Agency (EMA), for the validation of analytical methods [12]. The present review draws attention to nonmicellar chiral capillary electrokinetic chromatography (CEKC) as a well-established technique for enantioseparation. Methodological and application advances, for the use of the technique in the enantiomeric separation and enantiomeric impurity determination, are discussed, and new chiral selectors are reported. The successful use of Quality by Design is explored, and the application to elucidate the mechanism of enantiomeric separation and the enantiomer migration order (EMO) is critically reviewed with special highlights on challenges, solutions, and future aspects
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