Interaction of cyclodextrins with drugs. Chromatographic investigation using a cyclodextrin bonded-phase and its application to chiral separations

Summary

The interaction between cyclodextrin and the drug (1R,2S,3S,4S)-(5Z)-7-(3-((phenylsulfonyl)amino)bicyclo[2.2.1]hept-2-yl)hept-5-enoic acid ((+)-S-145), was studied using α-, β-, and γ-cyclodextrin bonded-phase columns. Retention behavior of (+)-S-145 on these columns revealed that the strength of inclusion was β→γ→α-cyclodextrin. Interaction between β-cyclodextrin and (+)-S-145 was found to increase as the proportion of carboxylic ion in the (+)-S-145 molecule increased. Comparison of binding capacities of these bondedsilica gels obtained by frontal analysis and surface coverage indicated that availability of the immobilized β- and γ-cyclodextrin was 20–25%. The synthesized β-cyclodextrin bonded-phase column was superior to that of commercial columns in terms of chiral separation of (±)-S-145. A typical usage of the β-cyclodextrin column is discussed for separation of (±)-S-145 in plasma samples.