Enantioseparation of β-blockers with two chiral centers by capillary electrophoresis using sulfated β-cyclodextrins

Abstract

Capillary electrophoresis methods for the enantioresolution of two beta-blockers possessing two chiral centers--labetalol and nadolol--were developed using electrokinetic chromatography. These methods were based on the addition of sulfated beta-cyclodextrins (S-betaCD) as chiral selectors to the background electrolyte (BGE). Different operating parameters (pH and ionic strength of the BGE, concentration of S-beta-CD) were investigated using a normal or reversed polarity mode. A complete resolution of the four isomers of labetalol was obtained either at the cathode or at the anode according to the pH of the BGE. The resolution of nadolol was observed whatever polarity of the applied voltage but a baseline separation of the four enantiomers within a time of analysis appropriate to routine assay was only obtained at the anode. This optimal separation was performed using high concentrations of chiral additive in an acidic pH buffer of low molarity. Besides the complete enantiomeric separation of the beta-blockers studied, the interest of the proposed methods is to permit a reversal of the migration order of the different enantiomers. This could be of high interest in quality control for the study of enantiomeric purity, which is now required for the development of drugs and chemicals.

Enantiomer migration order in chiral capillary electrophoresis

“…The most interesting feature of this technique is that the migration order of enantiomers can be reverted without affecting the enantioselective interactions in the separation system and just applying an additional nonenantioselective migration force. Such forces are many and of different nature as it has been summarized in the earlier review article [1] and employed in many research articles published in the recent years [32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Some of these examples are realized by reverting the polarity of the high-voltage supply.…”

Comparison of three S‐β‐CDs with different degrees of substitution for the chiral separation of 12 drugs in capillary electrophoresis

“…However, this was not true for the enantioseparation of anticholinergic agents, which got higher resolution values with two randomly substituted S‐β‐CDs (Figure b). These results seemed to confirm the fact that the enantioselectivity was affected by the DS of S‐β‐CD, and the optimum selector depended on the structures of the tested analytes were observed . Figure gives the electropherograms of (a) CLO and (b) ATP with three kinds of S‐β‐CDs at 20 g/L as chiral selectors.…”

A novel solid‐phase extraction–spectrofluorimetric method for the direct determination of atenolol in human urine

“…Various analytical methods have been developed for the determination of ATE in different pharmaceutical formulations, biological and environmental samples. These methods include spectrophotometry , spectrofluorimetry , GC , HPLC , capillary electrophoresis , voltammetry and LC‐MS/MS . With the exception of spectrophotometry and spectrofluorimetry, although the remaining methods have some advantages such as sensitivity and selectivity, they require expensive instrumentation, highly skilled operators and usually tedious sample pretreatment procedures in the analysis of biological samples.…”