Metabolite identification in early stage discovery molecule have a vast application in agricultural and pharmaceutical fields. However, it can be a very challenging task specially for compounds devoid of unique isotope pattern. Hydrogen/deuterium exchange−mass spectrometry (HDX−MS) is a rapidly evolving technique for analyzing structural features of proteins. In combination with MS techniques, hydrogen/deuterium (H/D) exchange can provide additional information for structural elucidation by determination of the number of exchangeable hydrogen atoms in a structure, which could be applied to the structure elucidation of small molecules for fast screening of the phase I hydroxylated metabolites. In this study we evaluated primary metabolite formed through <i>in vitro </i>assay for a set of representative commercially available small molecules. The combination of the H-D exchange process and the assay system is found to be a powerful tool for the study of challenging cases in structure elucidation and resulting in unambiguous metabolite identification. The study results demonstrated the importance of efficient H/D exchange and effectiveness of high-resolution mass spectrometry in combination with an online H/D exchange technique in rapid identification of drug metabolites, especially in discriminating hydroxylated metabolites.

Application of online hydrogen-deuterium exchange for fast screening and metabolite identification in drug and pesticide metabolism

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.