Ketopinic acid and diisoproylideneketogulonic acid as chiral ion-pair selectors in capillary electrophoresis: Enantiomeric impurity analysis of S-timolol and 1R,2S-ephedrine

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.