Rapid development of the enantiomeric separation of beta-blockers by capillary electrophoresis using an experimental design approach

A rapid method for determining the separation conditions for chiral resolut ion of eleven beta-blocking drug substances by capillary electrophoresis is described, using an experimental design approach. An acidic phosphate-trie thanolamine buffer and an uncoated fused-silica capillary were used for all experiments. Several modified cyclodextrins were applied as chiral selecto rs: sulfobutyl ether beta-cyclodextrin (SBE-PCD), dimethyl beta-cyclodextri n (DM-beta CD), carboxymethyl beta-cyclodextrin (CM-beta CD), and hydroxypr opyl beta-cyclodextrin (HP-beta CD). Two different fractional factorial exp erimental designs were applied: (1) a design examining four factors at thre e levels (3(4-2)) and (2) one examining three factors at two levels (2(3-1) ). The factors studied were: type of cyclodextrin, cyclodextrin concentrati on, pH of the background electrolyte and percentage of organic modifier. En ough resolution for the separation of the enantiomers and even for their qu antification was reached. The same scheme is proposed when a fast chiral se paration method needs to be developed for other drug families. (C) 1999 Els evier Science B.V. All rights reserved.