Comparison of chiral recognition capabilities of cyclodextrins for the separation of basic drugs in capillary zone electrophoresis.
The enantiomeric separation of some racemic anti-histamines and anti-malarials, namely (+/-)-pheniramine, (+/-)-brompheniramine, (+/-)-chlorpheniramine, (+/-)-doxylamine, and (+/-)-chloroquine, was investigated by capillary zone electrophoresis. The enantiomeric separation of five compounds was obtained by addition of approximately 7 mM (1%, w/v) sulfated-beta-cyclodextrin into the buffer as a chiral selector. The effects of sulfated-beta-cyclodextrin concentration and buffer pH on migration and resolution are discussed. Two other cyclodextrins, carboxyethylated-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin were also investigated. Four of the racemic compounds were resolved using 14 mM (2%, w/v) carboxyethylated-beta-cyclodextrin while 28 mM (4%, w/v) hydroxypropyl-beta-cyclodextrin resolved only two of them. It was found that the type of substituent and the degree of substitution on the rim of the CD structure played an important role in enhancing the chiral recognition. Cyclodextrins with negatively charged substituents and higher degree of substitution on the rim of the structure proved to give better resolution to the cationic racemic compounds compared with cyclodextrin with neutral substituents. This is due to the countercurrent mobility of the negatively charged cyclodextrin relative to the cationic analytes thus allowing for a smaller difference in interaction constants to achieve a successful resolution of enantiomers. Furthermore, lower concentrations of negatively charged cyclodextrins were necessary to achieve the equivalent resolutions as compared with the neutral ones.
Jin
L J
LJ
Department of Chemistry, National University of Singapore, Kent Ridge Crescent, Singapore.
Li
S F
SF
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000962:Antimalarials / Q000302:isolation & purification; D002738:Chloroquine / Q000302:isolation & purification; D002744:Chlorpheniramine / Q000302:isolation & purification; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006634:Histamine H1 Antagonists / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D013431:Sulfates / Q000737:chemistry; D047392:beta-Cyclodextrins
D000962:Antimalarials; D003505:Cyclodextrins; D006634:Histamine H1 Antagonists; D013431:Sulfates; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002744:Chlorpheniramine; D002738:Chloroquine