Chemistry” on HDX MS. 1 That review covered HDX MS applications from January 2012 through June 2014 and described the publications in terms of sector, geography, and topic. The present review was conceived with the same overall goal and to update the community on the status of HDX MS covering articles that appeared from July 1, 2014 through June 30, 2020 (the review period).

To get a sense of how the HDX MS field has evolved, we catalogued all articles on HDX MS in the review period. Each coauthor independently searched Pubmed using the search terms “hydrogen deuterium exchange mass spectrometry”, search results were combined, duplicates removed, and searching repeated multiple times by year using variations on the search terms [eg, deuterium exchange MS, HDX, HXMS, etc.] to find articles that were missed during the initial searches. We removed articles that were not primarily focused on proteins (eg, we removed HDX MS of peptides, sugars, and small molecules) and exchange that was not performed in solution, with the exception of solid-state HDX MS (as below, section on Methods Development: Pre-LC). Any article published such that a preprint or early edition was available and a DOI had been issued before June 30, 2020 was included. An Excel file with all articles that were included in the final catalog is available as Supporting Information. As we discovered, cataloguing the papers was a daunting task and the likelihood that some papers were missed in this process is not zero; we apologize in advance for those that were not found easily using this strategy. Some general statistics for the articles are shown in Figure 1. There were 902 items (mostly articles but also book chapters and even an entire book) identified in the review period, seeming higher than the 234 articles for the 2012− 2014 period previously reviewed. 1 When normalized to papers published per month (Figure 1 A), 2014− 2020 showed a general increasing trend, with monthly output in 2019− 2020 approximately double that of output in 2012− 2013. In our previous 1 review, we categorized HDX MS publications by sector, geography, and topic to better understand what was being done, where, and by whom. Thinking it would be valuable to compare this same categorization between the old period and the new period,