title: Enantioseparation of mandelic acid derivatives by high performance liquid chromatography with substituted β-cyclodextrin as chiral mobile phase additive and evaluation of inclusion complex formation.
abstract: The enantioseparation of ten mandelic acid derivatives was performed by reverse phase high performance liquid chromatography with hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as chiral mobile phase additives, in which inclusion complex formations between cyclodextrins and enantiomers were evaluated. The effects of various factors such as the composition of mobile phase, concentration of cyclodextrins and column temperature on retention and enantioselectivity were studied. The peak resolutions and retention time of the enantiomers were strongly affected by the pH, the organic modifier and the type of β-cyclodextrin in the mobile phase, while the concentration of buffer solution and temperature had a relatively low effect on resolutions. Enantioseparations were successfully achieved on a Shimpack CLC-ODS column (150×4.6mm i.d., 5μm). The mobile phase was a mixture of acetonitrile and 0.10molL(-1) of phosphate buffer at pH 2.68 containing 20mmolL(-1) of HP-β-CD or SBE-β-CD. Semi-preparative enantioseparation of about 10mg of α-cyclohexylmandelic acid and α-cyclopentylmandelic acid were established individually. Cyclodextrin-enantiomer complex stoichiometries as well as binding constants were investigated. Results showed that stoichiometries for all the inclusion complex of cyclodextrin-enantiomers were 1:1.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China; Laboratory of Bioseparation Technologies, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Tong
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Mangmang
authors.initials: M
authors.lastname: Shen
authors.affiliation: Laboratory of Bioseparation Technologies, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address: zyx@zjut.edu.cn.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Yan
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D008333:Mandelic Acids / Q000737:chemistry / Q000302:isolation & purification*; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D008333:Mandelic Acids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin; C037938:mandelic acid
keywords: Chiral separation; High performance liquid chromatography; Hydroxypropyl-β-cyclodextrin; Mandelic acid derivatives; Sulfobutyl ether-β-cyclodextrin