Enantiomeric resolution of some nonsteroidal antiinflammatory and anticoagulant drugs using beta-cyclodextrins by capillary electrophoresis

beta-cyclodextrin (CD) and its derivatives HP-beta-CD, DM-beta-CD, and TM-b eta-CD have been employed as chiral selectors for the separation of three n onsteroidal antiinflammatory drugs (NSAIDs) and anticoagulant at relatively low concentration (8-15 mM) by capillary zone electrophoresis (CZE). In th is study, baseline separation was achieved for ibuprofen, ketoprofen, napro xen, and warfarin. It was found that the addition of 0.1% hydroxypropyl met hyl cellulose (HPMC) was effective for separation. Under these conditions, the S-(+) enantiomer eluted before R-(-) in terms of ibuprofen; the calcula ted energy values obtained from the molecular modeling correlated well with the elution order. An equation for calculating the pK(a) values by capilla ry electrophoresis was introduced, and the pK(a) values of the four chiral drugs at 25 degrees C were obtained based on the equation. The value pK(a) + 0.5 is proposed to be the suitable pH of the background electrolyte for t he separation of chiral compounds containing a carboxylic group. Chirality 11:56-62, 1999. (C) 1999 Wiley-Liss, Inc.