948 (2002) 321–329 Journal of Chromatography A, www.elsevier.com / locate / chroma Prediction of selectivity for enantiomeric separations of uncharged compounds by capillary electrophoresis involving dual cyclodextrin systems * Adel M. Abushoffa, Marianne Fillet, Phillipe Hubert, Jacques Crommen ` Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liege, CHU, B 36, Avenue de l’ Hopital 1, ` B-4000 Liege, Belgium Abstract The single-isomer polyanionic cyclodextrin (CD) derivative heptakis-6-sulfato-b-cyclodextrin (HSbCD) has been tested as chiral additive for the enantioseparation of non-steroidal anti-inflammatory drugs, such as fenoprofen, flurbiprofen, ibuprofen and ketoprofen, in capillary electrophoresis, using a pH 2.5 phosphoric acid–triethanolamine buffer in the reversed polarity mode. In most cases, the enantiomers of these acidic compounds, present in uncharged form at that pH, were only poorly resolved with HSbCD alone. However, the use of HSbCD in combination with the neutral CD derivative, heptakis-(2,3,6-tri-O-methyl)-b-cyclodextrin (TMbCD), which has a particularly high enantioselectivity towards these compounds, has led to complete enantioresolution in reasonably low migration times in most cases. Affinity constants for the enantiomers with the two cyclodextrins were determined, using linear regression in a two-step approach. Affinity constants with the charged HSbCD were first calculated in single systems while those with the neutral TMbCD were determined in dual systems. Selectivity for the enantiomeric separation of these compounds in dual CD systems could be predicted using recently developed mathematical models.  2002 Elsevier Science B.V. All rights reserved. Keywords: Enantiomer separation; Pharmaceutical analysis; Selectivity; Mathematical modelling; Cyclodextrins; Profens; Nonsteroidal anti-inflammatory drugs 1. Introduction determination. Over the past few years, capillary electrophoresis (CE) has been proved to be a power- The enantioseparation of chiral compounds is of ful tool for chiral analysis, as it provides high great importance in the pharmaceutical field, where a separation efficiencies together with rapid method wide number of drugs have one or more chiral development and low consumption of additives [1– centers and are used as racemic mixtures.Very often, 8]. the pharmacological activity and metabolism of the A number of chiral compounds have been enan- two enantiomers are different, therefore, appropriate tioseparated using various kinds of chiral selectors in analytical methods are required for their individual CE. Among these selectors, cyclodextrins (CDs) have been shown to be broad spectrum chiral selectors due to their physicochemical properties and *Corresponding author. Tel.: 132-4-366-4346; fax: 132-4- commercial availability in native and derivatized 366-4347. E-mail address: jcrommen@ulg.ac.be (J. Crommen). forms [9–11]. However, the use of single cyclo- 0021-9673 / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. PII: S0021-9673(01)01371-1