title: Direct enantioseparation of underivatized aliphatic 3-hydroxyalkanoic acids with a quinine-based zwitterionic chiral stationary phase.
abstract: 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.
authors.affiliation: 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.
authors.forename: Federica
authors.initials: F
authors.lastname: Ianni
authors.affiliation: 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.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Pataj
authors.affiliation: Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Gross
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Roccaldo
authors.initials: R
authors.lastname: Sardella
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Natalini
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Währinger Strasse 38, 1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lindner
authors.affiliation: Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany. Electronic address: michael.laemmerhofer@uni-tuebingen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Lämmerhofer
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005227:Fatty Acids / Q000737:chemistry*; D011803:Quinine / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D005227:Fatty Acids; D011803:Quinine
keywords: 3-Hydroxyalkanoic acids, liquid chromatography; Cinchona-based zwitterionic chiral stationary phase; Enantiomer separation; Natural compounds, polar-organic mode; Underivatized 3-hydroxycarboxylic acids