The Use of Dual Cyclodextrin Chiral Selector Systems in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: An Overview.

Gabriel Hancu,Gergő Tóth,Lajos Attila Papp,Hajnal Kelemen

doi:10.3390/molecules26082261

Abstract

Cyclodextrin (CD) derivatives are the most efficient and frequently used chiral selectors (CSs) in capillary electrophoresis (CE). There are situations when the use of a single CD as CS is not enough to obtain efficient chiral discrimination of the enantiomers; in these cases, sometimes this problem can be resolved using a dual CD system. The use of dual CD systems can often dramatically enhance enantioseparation selectivity and can be applied for the separation of many analytes of pharmaceutical interest for which enantioseparation by CE with another CS systems can be problematic. Usually in a dual CD system an anionic CD is used together with a neutral one, but there are situations when the use of a cationic CD with a neutral one or the use of two neutral CDs or even two ionized CDs can be an efficient solution. In the current review we present general aspects of the use of dual CD systems in the analysis of pharmaceutical substances. Several examples of applications of the use of dual CD systems in the analysis of pharmaceuticals are selected and discussed. Theoretical aspects regarding the separation of enantiomers through simultaneous interaction with the two CSs are also explained. Finally, advantages, disadvantages, potential and new direction in this chiral analysis field are highlighted.

Highlights

Published: 14 April 2021More than half of the pharmaceutical substances currently used in therapy are chiral, only about 25% are used in the form of a pure enantiomer
This work troscopy (2-D ROESY-nuclear magnetic resonance spectroscopy (NMR)) experiments were applied to characterize complex forunderlines the challenges analysts must overcome in developing chiral separations as there mation; the results indicated the inclusion of the benzene sulfonamide moiety of sulis a large diversity of CDs used as chiral selectors (CSs) which can be mixed in multiple combinations [55]
To choose an efficient dual CD system, and explain chiral separation, analysts must consider both chiral interactions which occurs at molecular level and chiral recognition which leads to chiral discrimination

Summary

Introduction

More than half of the pharmaceutical substances currently used in therapy are chiral, only about 25% are used in the form of a pure enantiomer. The properties of individual enantiomers of a racemic mixture should be studied and characterized individually; and the stereoisomeric composition of an optically active drug must be verified from pharmacokinetic, pharmacologic, and toxicologic point of view [2] These regulations have major implications in the development of new analytical methods for chiral drug control. When dual CD systems are used often there are differences in the complexation mechanisms of the two CDs with the enantiomers of the chiral analyte, which are translated into differences between complexation stabilities, chiral identification patterns, and influence on the electrophoretic mobility of the analytes [17]. The current review focuses on the use of dual CD systems for the analysis of pharmaceuticals and particular features of CD mixture use in CE, presenting specific applications of in the enantioseparation of analytes of interest from different matrices

Applications of Dual CD Systems in the Analysis of Pharmaceuticals

Discussion

Conclusions