In addition to data dependent acquisition (DDA), data independent acquisition (DIA) LC-MS workflows such as SWATH MS using CID on fast-acquiring QqTOF platforms have gained interest for untargeted screening. Ideally, performing all three activation methods within a single LC-MS run using either DDA or DIA would be highly beneficial. However, due to current software and technical limitations, this is not yet feasible. The strategy applied, as shown in Figure and, is to perform a general screening in a first LC-MS/MS analysis using DIA SWATH MS with CID to detect known analytes and unknowns such as metabolites or contaminants. In a second step, in addition to a full scan acquisition, a targeted LC-MS/MS analysis is performed using scheduled MRM HR CID/EAD/UVPD using all three fragmentation methods in less than one second without compromising LC resolution . The TOF MS-Zeno trapping scheduled MRM HR method is illustrated in Figure . Each block unit incorporates CID, EAD, and UVPD MS/MS and the TOF MS spectra for each analyte. This setup allows four MRM HR CID/EAD/UVPD blocks to overlap, each with a 235 msec accumulation time.