While aliphatic 2-hydroxyalkanoic acids have been more or less successfully enantioseparated with various chiral stationary phases by HPLC and GC, analogous applications on underivatized aliphatic 3-hydroxyalkanoic acids are completely absent in the scientific literature. With the aim of closing this gap, the enantioseparation of 3-hydroxybutyric acid, 3-hydroxydecanoic acid and 3-hydroxymyristic acid has been performed with two ion-exchange type chiral stationary phases (CSPs): one containing the anion-exchange type tert-butyl carbamoyl quinine chiral selector motif (Chiralpak QN-AX), and the other carrying the new zwitterionic variant based on trans-(S,S)-2-aminocyclohexanesulfonic acid-derivatized quinine carbamate (Chiralpak ZWIX(+)) as the chiral selector and enantiodiscriminating element, respectively. The zwitterionic enantiorecognition material provided better results in terms of enantioselectivity and resolution compared to the anion-exchanger CSP at reduced retention times due to the intramolecular counterion effect imposed by the sulfonic acid moiety and its competition with the 3-hydroxyalkanoic acid analyte for ionic interaction at the quininium-anion exchanger site. It is thus recommended as the CSP of first choice for enantioseparations of the class of aliphatic 3-hydroxyalkanoic acids. With use of polar organic eluent composed of ACN/MeOH/AcOH - 95/5/0.05 (v/v/v), a good compromise in terms of analysis time and enantioresolution quality was accomplished. The major experimental variables have been investigated for optimization of the resolution and allowed to derive information on the enantiorecognition mechanism. Corresponding Chiralpak ZWIX(-), based on pseudo-enantiomeric selector derived from quinidine and trans-(R,R)-2-aminocyclohexanesulfonic acid with opposite configurations provided reversed enantiomer elution orders. It has further to be stressed that these separations can be obtained with mass spectrometry compatible mobile phases.

Department of Analytical Chemistry University of Vienna Währinger Strasse 38 1090 Vienna Austria

Department of Pharmaceutical Sciences University of Perugia Via del Liceo 1 06123 Perugia Italy

Department of Pharmaceutical Sciences University of Perugia Via del Liceo 1 06123 Perugia Italy; Institute of Pharmaceutical Sciences University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany

Institute of Pharmaceutical Sciences University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany

Institute of Pharmaceutical Sciences University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany; Regional Centre of Advanced Technologies and Materials Department of Analytical Chemistry Faculty of Science Palacký University 17 listopadu 12 771 46 Olomouc Czech Republic

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