Electron-transfer dissociation (ETD) is a method of fragmenting ions in a mass spectrometer. Similar to electron-capture dissociation, ETD induces fragmentation of cations (e.g. peptides or proteins) by transferring electrons to them. The technique only works well for higher charge state ions, however relative to collision-induced dissociation (CID), ETD is advantageous for the fragmentation of longer peptides or even entire proteins.

For biopharmaceutical characterization, ETD is a powerful fragmentation technique for determining modification sites of labile post-translational modifications (PTMs), which are often difficult to characterize using CID.

ETD can be implemented and performed on a hybrid quadrupole time-of-flight MS with ion mobility, where a supply of reagent is delivered to the nano ESI source and a high- voltage discharge pin generates the reagent anions. Analyte cations are generated by infusion or from a nanoACQUITY UPLC system.

For ETD, the ion source polarity and the quadrupole set mass are sequentially switched to deliver anions and cations into the TRAP travelling wave (T-Wave) ion guide where they interact to form ETD product ions. Product ions are optionally separated by ion mobility in the IMS T-Wave ion guide or are accelerated into the TRANSFER T-Wave ion guide to cause second-generation CID ions prior to mass analysis in the TOF. New software that uses both a survey scan and charge state recognition can alternatively decide to perform ETD in the TRAP T-Wave for the higher charge states or CID in the TRANSFER T-Wave for the lower ones.