Enantiomeric separation of drugs by mucopolysaccharide-mediated electrokinetic chromatography.
Chondroitin sulfate C (sodium salt) and heparin (sodium salt), which are both mucopolysaccharides and natural components, have been employed as chiral selectors in electrokinetic chromatography (EKC) for the separation of enantiomers of drugs. These additives are charged, linear, sulfated polysaccharides having large mass. Ionic and hydrophobic interactions are probably the bases for the separation. Among tested drugs that are electrically neutral or basic, trimetoquinol, diltiazem, and their related compounds were successfully enantioseparated by EKC with mucopolysaccharides, especially with chondroitin sulfate C. The choices of pH and the concentration of mucopolysaccharides were found to be important for improvement of enantioselectivity. The acidic buffer solutions were effective for enantioseparation of the solutes in the chondroitin sulfate C system, although no migration of the basic drugs was observed in the heparin system. The results were compared with the enantiomeric separation by EKC with dextran sulfate (sodium salt). The method using chondroitin sulfate C was successfully applied to the optical purity testing of the drug substances.
Nishi
H
H
Analytical Research Laboratory, Tanabe Seiyaku Company, Ltd., Osaka, Japan.
Nakamura
K
K
Nakai
H
H
Sato
T
T
D002845:Chromatography; D004563:Electrochemistry; D006025:Glycosaminoglycans / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D013237:Stereoisomerism
D006025:Glycosaminoglycans; D004364:Pharmaceutical Preparations