Rapid Solution-Phase Hydrogen/Deuterium Exchange for Metabolite Compound Identification

  • Sandra N. Majuta
  • Chong Li
  • Kinkini Jayasundara
  • Ahmad Kiani Karanji
  • Kushani Attanayake
  • Nandhini Ranganathan
  • Peng Li
  • Stephen J. ValentineEmail author
Focus: Ion Mobility Spectrometry (IMS): Research Article


Rapid, solution-phase hydrogen/deuterium exchange (HDX) coupled with mass spectrometry (MS) is demonstrated as a means for distinguishing small-molecule metabolites. HDX is achieved using capillary vibrating sharp-edge spray ionization (cVSSI) to allow sufficient time for reagent mixing and exchange in micrometer-sized droplets. Different compounds are observed to incorporate deuterium with varying efficiencies resulting in unique isotopic patterns as revealed in the MS spectra. Using linear regression techniques, parameters representing contribution to exchange by different hydrogen types can be computed. In this proof-of-concept study, the exchange parameters are shown to be useful in the retrodiction of the amount of deuterium incorporated within different compounds. On average, the exchange parameters retrodict the exchange level with ~ 2.2-fold greater accuracy than treating all exchangeable hydrogens equally. The parameters can be used to produce hypothetical isotopic distributions that agree (± 16% RMSD) with experimental measurements. These initial studies are discussed in light of their potential value for identifying challenging metabolite species.


Metabolomics Hydrogen-deuterium exchange Compound identification 



We are grateful for financial support from the National Science Foundation (CHE-1553021).

Supplementary material

13361_2019_2163_MOESM1_ESM.docx (296 kb)
ESM 1 (DOCX 295 kb)


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© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.C. Eugene Bennett Department of ChemistryWest Virginia UniversityMorgantownUSA

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