Insight into the chiral recognition of warfarin enantiomers by epichlorhydrin/beta-cyclodextrin polymer-based supports: determination of stoichiometry and stability of warfarin/beta-cyclodextrin polymer complexes.
The complexation of warfarin (W) enantiomers by a hydrosoluble high-molecular-weight beta-cyclodextrin/epichlohydrin polymer (EP/beta-CD polymer) was studied using HPLC with a mobile phase of methanol/0.1 M Na acetate/acetic acid (pH 4) at 22 degrees C. It was found that the complexes (W/beta-CD unit) have a 1:1 stoichiometry. The stability constants of the complex involving each enantiomer and the polymer beta-CD units were determined in the mobile phase, and the highest stability of the complex (S-warfarin/beta-CD unit) was observed. From the chromatographic separations of warfarin enantiomers on different beta-CD or its derivative supports, we have deduced the role of the simultaneous presence of several glyceryl (-O-CH(2)-CHOH-CH(2)-O-) and dihydroxypropyl (-O-CH(2)-CHOH-CH(2)OH) groups on one beta-CD ring in promoting the chiral recognition of warfarin enantiomers.
Thuaud
Nicole
N
Laboratoire de Recherche sur les Polymères, Université de Paris XII, UMR CNRS C 7581, 2-8 rue Henri Dunant, F-94320 Thiais, France.
Sebille
Bernard
B
Renard
Estelle
E
D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D003505:Cyclodextrins / Q000737:chemistry*; D004811:Epichlorohydrin / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism; D014859:Warfarin / Q000032:analysis / Q000737:chemistry* / Q000145:classification / Q000302:isolation & purification*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D012996:Solutions; D047392:beta-Cyclodextrins; D004811:Epichlorohydrin; D014859:Warfarin; C031215:betadex