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

• Published in: Journal of the American Society for Mass Spectrometry 2019-06, Vol.30 (6), p.1102-1114
• Main Authors: Majuta, Sandra N., Li, Chong, Jayasundara, Kinkini, Kiani Karanji, Ahmad, Attanayake, Kushani, Ranganathan, Nandhini, Li, Peng, Valentine, Stephen J.
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Bioinformatics; Biotechnology; Chemistry; Chemistry and Materials Science; Deuterium; Deuterium - chemistry; Deuterium Exchange Measurement - economics; Deuterium Exchange Measurement - instrumentation; Equipment Design; Exchanging; Focus: Ion Mobility Spectrometry (IMS): Research Article; Hydrogen; Hydrogen - chemistry; Ionization; Mass spectrometry; Mass Spectrometry - economics; Mass Spectrometry - instrumentation; Metabolites; Metabolomics - economics; Metabolomics - instrumentation; Organic Chemistry; Parameters; Proteomics; Reagents; Time Factors
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1007/s13361-019-02163-0

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.