title: Ketopinic acid and diisoproylideneketogulonic acid as chiral ion-pair selectors in capillary electrophoresis. Enantiomeric impurity analysis of S-timolol and 1R,2S-ephedrine.
abstract: 1S,4R-(+)-ketopinic acid [(+)-KPA] has been introduced as a chiral selector for the separation of pharmacologically active amines by non-aqueous capillary electrophoresis (NACE). (+)-KPA gave enantioresolution for most of the compounds previously separated by 2R,3S,4R,5S-(-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid [(-)-DIKGA], but with a reversed migration order. A complete enantioresolution (Rs=4.2) was obtained for timolol, a compound that could not be resolved using (-)-DIKGA as the selector. Thus, (+)-KPA was evaluated for the enantiomeric purity determination of S-timolol. A method based on pre-concentration by transient isotachophoresis (tITP) provided a limit of detection (LOD) of 0.2% R-timolol in S-timolol samples. Because of the lack of enantioresolution of ephedrine when (+)-KPA was used as the selector, a method with (-)-DIKGA has been developed and validated for determination of the enantiomeric purity of the 1R,2S enantiomer. The method gave good precision and accuracy with an LOD (S/N=3) of 0.033% for the enantiomeric impurity 1S,2R-ephedrine.
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hedeland
authors.forename: Jenni
authors.initials: J
authors.lastname: Lehtinen
authors.forename: Curt
authors.initials: C
authors.lastname: Pettersson
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D004809:Ephedrine / Q000032:analysis*; D007659:Ketones / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013400:Sugar Acids / Q000737:chemistry*; D013999:Timolol / Q000032:analysis*
chemical_list: C441632:2,3-4,6-di-O-isopropylidene-2-ketogulonic acid; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D007659:Ketones; D013400:Sugar Acids; C431983:ketopinic acid; D013999:Timolol; D004809:Ephedrine