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Rapid development of the enantiomeric separation of beta-blockers by capillary electrophoresis using an experimental design approach.
Authors:M G Vargas  Y Vander Heyden  M Maftouh  D L Massart
Institution:Department of Pharmaceutical and Biomedical Analysis, Vrije Universiteit Brussel, Belgium.
Abstract:A rapid method for determining the separation conditions for chiral resolution of eleven beta-blocking drug substances by capillary electrophoresis is described, using an experimental design approach. An acidic phosphate-triethanolamine buffer and an uncoated fused-silica capillary were used for all experiments. Several modified cyclodextrins were applied as chiral selectors: sulfobutyl ether beta-cyclodextrin (SBE-beta CD), dimethyl beta-cyclodextrin (DM-beta CD), carboxymethyl beta-cyclodextrin (CM-beta CD), and hydroxypropyl beta-cyclodextrin (HP-beta CD). Two different fractional factorial experimental designs were applied: (1) a design examining four factors at three levels (3(4-2)) and (2) one examining three factors at two levels (2(3-1)). The factors studied were: type of cyclodextrin, cyclodextrin concentration, pH of the background electrolyte and percentage of organic modifier. Enough resolution for the separation of the enantiomers and even for their quantification was reached. The same scheme is proposed when a fast chiral separation method needs to be developed for other drug families.
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