Chiral separation of disease biomarkers with 2-hydroxycarboxylic acid structure

Chiral 2-hydroxycarboxylic acids are compounds that have been linked to particular diseases and are putative biomarkers with some diagnostic potential. The importance of identifying whether a particular enantiomer is related to certain diseases has been encouraged recently. However, in many cases it has not yet been elucidated whether there are stereochemical implications with respect to these biomarkers and whether their enantioselective analysis provides new insights and diagnostic potential. In this study 13 disease-related chiral 2-hydrocarboxylic acids were studied for their chiral separation by high-performance liquid chromatography on three cinchona alkaloid-derived chiral stationary phases. From a subgroup of eight 2-hydroxymonocarboxylic acids, baseline resolution could be achieved and inversion of elution order by exchanging tert-butylcarbamoyl quinidine chiral stationary phase (Chiralpak QD-AX) for the corresponding quinine analogue (Chiralpak QN-AX) is shown for seven of them. Furthermore, conditions for chiral separation of the 2-hydroxydicarboxylic acids, citramalic acid, 2-isopropylmalic acid, and 2-hydroxyadipic acid are reported and compared to the previous reported conditions for 2-hydroxyglutaric acid and malic acid.