Prediction of selectivity for enantiomeric separations of uncharged compounds by capillary electrophoresis involving dual cyclodextrin systems.
The single-isomer polyanionic cyclodextrin (CD) derivative heptakis-6-sulfato-beta-cyclodextrin (HSbetaCD) 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 HSbetaCD alone. However, the use of HSbetaCD in combination with the neutral CD derivative, heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMbetaCD), 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 HSbetaCD were first calculated in single systems while those with the neutral TMbetaCD 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.
Abushoffa
Adel M
AM
Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liège, CHU, B 36, Avenue de l'Hopital 1, B-4000 Liège, Belgium.
Fillet
Marianne
M
Hubert
Phillipe
P
Crommen
Jacques
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000302:isolation & purification; D002021:Buffers; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D015233:Models, Statistical; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002021:Buffers; D003505:Cyclodextrins; D007202:Indicators and Reagents; D047392:beta-Cyclodextrins; C475632:heptakis-6-sulfato-beta-cyclodextrin; C000609658:heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin