Distinguishing Oligosaccharide Isomers Using Far-Infrared Ion Spectroscopy: Identification of Biomarkers for Inborn Errors of Metabolism

Anal Chem. 2023 Jul 4;95(26):9787-9796. doi: 10.1021/acs.analchem.3c00363. Epub 2023 Jun 21.

Abstract

Distinguishing isomeric saccharides poses a major challenge for analytical workflows based on (liquid chromatography) mass spectrometry (LC-MS). In recent years, many studies have proposed infrared ion spectroscopy as a possible solution as the orthogonal, spectroscopic characterization of mass-selected ions can often distinguish isomeric species that remain unresolved using conventional MS. However, the high conformational flexibility and extensive hydrogen bonding in saccharides cause their room-temperature fingerprint infrared spectra to have broad features that often lack diagnostic value. Here, we show that room-temperature infrared spectra of ion-complexed saccharides recorded in the previously unexplored far-infrared wavelength range (300-1000 cm-1) provide well-resolved and highly diagnostic features. We show that this enables distinction of isomeric saccharides that differ either by their composition of monosaccharide units and/or the orientation of their glycosidic linkages. We demonstrate the utility of this approach from single monosaccharides up to isomeric tetrasaccharides differing only by the configuration of a single glycosidic linkage. Furthermore, through hyphenation with hydrophilic interaction liquid chromatography, we identify oligosaccharide biomarkers in patient body fluid samples, demonstrating a generalized and highly sensitive MS-based method for the identification of saccharides found in complex sample matrices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Humans
  • Ions
  • Isomerism
  • Metabolism, Inborn Errors*
  • Monosaccharides
  • Oligosaccharides* / chemistry
  • Spectrophotometry, Infrared

Substances

  • Oligosaccharides
  • Monosaccharides
  • Biomarkers
  • Ions