Hydrogen/deuterium exchange mass spectrometry in the world of small molecules.

The combined use of hydrogen/deuterium exchange (HDX) and mass spectrometry (MS), referred to as HDX‐MS, is a powerful tool for exploring molecular edifices and has been used for over 60 years. Initially for structural and mechanistic investigation of low‐molecular weight organic compounds, then to study protein structure and dynamics, then, the craze to study small molecules by HDX‐MS accelerated and has not stopped yet. The purpose of this review is to present its different facets with particular emphasis on recent developments and applications. Reversible H/D exchanges of mobilizable protons as well as stable exchanges of non‐labile hydrogen are considered whether they are taking place in solution or in the gas phase, or enzymatically in a biological media. Some fundamental principles are restated, especially for gas‐phase processes, and an overview of recent applications, ranging from identification to quantification through the study of metabolic pathways, is given. [ABSTRACT FROM AUTHOR]