Simultaneous separation and enantioresolution of racemic local anesthetic drugs by capillary zone electrophoresis with Tween 20 and methyl-β-cyclodextrin as selectors, employing a double plug technique

Abstract

A new approach for simultaneous chiral and achiral separations by capillary zone electrophoresis is described. Two adjacent selector plugs, consisting of Tween 20 as an achiral and methyl-beta-cyclodextrin (CD) as a chiral selector, are employed and four related local anesthetics are used as model compounds. The principles of the partial filling technique, whereby the capillary is filled with the chiral selector solution followed by the micellar solution at different plug lengths and concentrations, prior to application of the solutes, was employed. During the run both capillary ends were dipped in a simple buffer, i.e., one without additives. The two separation media worked independently without any interaction. Separation of the solutes and their enantiomers was regulated by adjusting both the concentration and plug length (PL) of the micellar solution in the capillary, employing methyl beta-CD as chiral selector either at 38 or 76 mM. The solutes were separated on the basis of their affinity towards the micellar phase before they reached the methyl-beta-CD plug for enantioseparation. In the absence of the micellar plug, the enantiomers of prilocaine overlapped those of bupivacaine. The solutes and their enantiomers were completely separated by employing two adjacent plugs consisting of 100 mM Tween 20 solution (PL approximately 10 cm) and methyl-beta-CD solution at either 38 or 76 mM (PL approximately 30 cm).

Principle and applications of the partial filling technique in capillary electrophoresis

“…The relationship between the plug length and migration time can be expressed by the following equation [42]:…”

“…In the first demonstration of this principle four local anaesthetics and their enantiomers were separated combining two adjacent selector plugs, consisting of Tween | 20 as an achiral and methyl-fi-cyclodextrin as a chiral selector [42]. In the first demonstration of this principle four local anaesthetics and their enantiomers were separated combining two adjacent selector plugs, consisting of Tween | 20 as an achiral and methyl-fi-cyclodextrin as a chiral selector [42].…”

Chiral Separations

“…Using carboxymethyl-β-cyclodextrin, Chankvetadze et al, demonstrated the potential of flow-counterbalanced capillary electrophoresis (FCCE) to increase selectivity for binary mixtures (38). The following applications using methylated cyclodextrin derivatives were reported: pressure supported CEC using capillaries packed with permethyl-β-cyclodextrin (38,40); separation of hexobarbital using a dual chiral recognition cyclodextrin derivatives (41); resolution of local anesthetic drugs using Tween 20 and methyl-β-cyclodextrin (42); nonaqueous separation of basic analytes using heptakis(2,3-dimethyl-6-sulfato)-β-cyclodextrin (43,44); determination of aspartic acid in biosamples (45); determination of salbutamol enantiomers and its application to dissolution samples (46); separation of numerous racemic drugs (47); and determination of binding constants between enantiomers of orciprenaline and methyl-β-cyclodextrin (48).…”

Rapid chiral separation and impurity determination of ropivacaine and bupivacaine by Densitometry-HPTLC, using mucopolysaccharide as chiral mobile phase additive

“…Different analytical methods have been developed for separation of enantiomers. Chiral separation by capillary electrophoresis (CE) using a variety of chiral selectors have been reported [7][8][9][10]. Among them cyclodextrins and their derivatives are the most frequently employed [11].…”