Chiral separation of disease biomarkers with 2‐hydroxycarboxylic acid structure

Abstract

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.

Enantioselectivity Effects in Clinical Metabolomics and Lipidomics

“…Chiral hydroxycarboxylic acids (HAs) have been related as biomarkers to some, but not only, metabolic diseases [ 35 , 36 , 37 ]. As with the amino acids, the ability to quantify the HAs enantiomers in the metabolome is essential [ 38 , 39 ].…”

“…Methods for enantioselective separation of 2-hydroxy and 3-hydroxy-derivatives have been described using chiral columns either by gas chromatography coupled to mass spectrometry (GC-MS) [ 41 ] or liquid chromatography coupled to mass spectrometry (LC-MS) [ 36 , 42 , 43 ] approaches. The separation of 3-HAs, from hexanoic to myristic acid, were separated in a CHIRALPAK IA-U (amylose tris (3,5-dimethylphenylcarbamate) immobilized onto a 1.6 mm silica) with resolution increasing with the chain length.…”

Chiral Stationary Phases for Liquid Chromatography: Recent Developments

“…It is important to highlight that recent applications of this type of CSPs were diversified, with the focus, mainly, on the application of anion and zwitterionic-type CSPs with amino acids [221,222,223,224,225].…”

Multi-Dimensional High-Performance Liquid Chromatographic Determination of Chiral Amino Acids and Related Compounds in Real World Samples

“…However, with the progress of analytical technologies, the existence of the minor enantiomers in living beings including humans has been reported and the differences in their concentrations have been found in various diseases [67][68][69]. Until now, various methods including CE [70,71], GC [72,73] and LC [74][75][76][77][78][79][80] have been developed for the enantioselective analysis of LA and 3HB, and multi-dimensional HPLC is useful like chiral amino acid analysis.…”