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 focus on a set of original data obtained with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TM-beta-CD) as the chiral solvating agent (CSA). The enantioseparation of 86 drugs by capillary zone electrophoresis in the presence of this CSA was successful for 47 drugs. The migration separation factors (alpham) and the migration retardation factors (Rm) were compared with those 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)-alpha-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 data. A substructure 4H was found in the analyte structure that has a significant influence on the analytes' behaviour. Thus, analytes bearing the substructure 4H do not only have a strong affinity to the CDs but also a high rate 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 drugs. Sterical considerations point to the significance of side-on-binding versus inclusion in the cavity of the host. In addition to the findings from the screening program, numerous references to the literature are given.
Koppenhoefer
B
B
Institute of Organic Chemistry, University of Tübingen, Germany. koppenhoefer@uni-tuebingen.de
Zhu
X
X
Jakob
A
A
Wuerthner
S
S
Lin
B
B
D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification*
D003505:Cyclodextrins; D004364:Pharmaceutical Preparations