Separation of drug enantiomers by capillary electrophoresis in the presence of neutral cyclodextrins

This is a selected review, highlighting our results obtained in an extended screening program ("The German-Chinese Drug Screening Program"), with a fo cus on a set of original data obtained with heptakis(2,3,6-tri-O-methyl)-be ta-cyclodextrin(TM-beta-CD) as the chiral solvating agent (CSA). The enanti oseparation of 86 drugs by capillary zone electrophoresis in the presence o f this CSA was successful for 47 drugs. The migration separation factors (a lpha(m)) and the migration retardation factors (R-m) were compared with tho se found for native beta-cyclodextrin (beta-CD). The patterns thus obtained were also compared with those observed for hexakis(2,3,6-tri-O-methyl)-alp ha-CD (TM-alpha-CD) and octakis(2,3,6-tri-O-methyl)-gamma-CD (TM-gamma-CD), respectively. From the statistical data, it can be concluded that there is a remarkable influence of the analyte structure on the electrophoretic dat a. A substructure 4H was found in the analyte structure that has a signific ant influence on the analytes' behaviour. Thus, analytes bearing the substr ucture 4H do not only have a strong affinity to the CDs but also a high rat e of success of chiral separation in all systems reviewed. In light of this , the different ring sizes of native cyclodextrins (alpha-, beta- and gamma -CD) readily explain their behaviour towards a limited test set of chiral d rugs. Sterical considerations point to the significance of side-on-binding versus inclusion in the cavity of the host. In addition to the findings fro m the screening program, numerous references to the Literature are given. ( C) 2000 Elsevier Science B.V. All rights reserved.