Comparison of dissociation of ions in an electrospray source, or a collision cell in tandem mass spectrometry

Electrospray ionization (ESI) is a soft ionization technique well suited for producing gas phase ions of biological macromolecules. The use of ESI when combined with collision-induced dissociation and mass analysis can give structural information about biomolecules. Traditionally, collisional fragmentation is carried out by tandem mass spectrometry. Several commercially available instruments permit tandem mass spectrometric experiments in space, in time or by post-source decay. Parameters influencing these processes and some applications are discussed in this article. It has been observed that in nearly all API sources, fragmentation of ions can arise by increasing the potential difference applied to the inlet and outlet orifices in the sampling region of the electrospray source kept under low vacuum. This process, called by variety of names, such as in-source collision-induced dissociation (CID), up-front CID, cone-voltage CID or nozzle-skimmer dissociation, is less well understood than the traditional tandem mass spectrometric technique. Thanks to in-source CID, it is possible to obtain structural information with a single quadrupole instrument or to achieve a method close to MS/MS/MS with a triple quadrupole instrument. Results from a few studies comparing in-source CID in an electrospray ion source and CID in the collision gas cell of a tandem mass spectrometer have been published. These studies show that results from the both processes are generally comparable. The advantages and the drawbacks of each technique will be developed thereafter. In this article, the comparisons are reviewed and suggestions are made to help the reader to make a choice between the two fragmentation processes depending on the nature of the sample.