We have been using fast scanning TripleTOF systems to analyze a variety of post-translational modifications (PTMs) using both data-independent acquisitions (DIA) and more recently multiple reaction monitoring-high resolution (MRM-HR) to identify, characterize and quantify PTM-containing peptides in a high-throughput format. While rich information has been obtained using traditional CID fragmentation approaches, many of the modifications we study are highly labile and difficult to characterize.