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

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.

Keywords: capillary electrophoresis; chiral selectors; chiral separation; cyclodextrins; dual cyclodextrin system.

Figure 1

Electropherogram of 5 mg/mL S-CIT oxalate containing approximately 2.4% R-CIT and 0.1% of citadiol enantiomers (1—R-CIT, 2—S-CIT, 3—S-citadiol, 4—R-citadiol, OX—acid oxalic, IS—internal standard (salicylic acid); experimental conditions: 20 mM phosphate BGE, pH 2.5, CS 22 mg/mL S-β-CD + 0.5 mg/mL β-CD, −20 kV voltage; 28 °C temperature; 50 mbar/5 s injection, detection at 205 nm) Reprinted from Sungthong et al. [41] with permission from Elsevier.

Figure 2

Chiral separation of tapentadol enantiomers by CE in single and dual CD systems ((A)—CS 0.5% HP-β-CD; (B)—CS 5% HP-γ-CD; (C)—CS 0.5% HP-β-CD + 5% HP-γ-CD; experimental conditions: 50 mM phosphate BGE, pH 2.5, −25 kV voltage; 15 °C temperature; 25 mbar/5 s injection, detection at 210 nm) Reprinted from Znaleziona et al. [50] with permission from Elsevier.

Figure 3

Chiral separation of rabeprazole enantiomers by CE in single and dual CD systems ((A)—CS 15 mM SBE-β-CD, (B)—CS 15 mM SBE-β-CD/30 mM γ-CD; experimental conditions: 25 mM phosphate BGE, pH = 7.0, +20 kV voltage; 18 °C temperature; 50 mbar/3 s injection, detection at 210 nm).