The most common LC/MS/MS ionization technique in the clinical laboratory is electrospray ionization (ESI). In contrast to electron ionization (EI) used in GC/MS, ESI produces much simpler mass spectra because the ionization and fragmentation is produced with much lower energy (this called 'soft ionization').
In ESI, the liquid sample stream exiting the column enters a heated probe that has a voltage applied to it. The difference in potential creates ions, either positive ions or negative ions, depending on the mode selected. Opiates, amphetamines, benzodiazepines, and tricyclic antidepressants are analyzed in positive mode, whereas barbiturates, THC, and ethyl glucuronide are analyzed in negative mode.
A heated nitrogen flow surrounds the probe and nebulizes the mobile phase as it exits. There are also heaters external to the probe that help speed up evaporation. As the mobile phase is nebulized, it is converted to very minute droplets of liquid containing the ions. As the droplets proceed into the source, they begin to get smaller and smaller as they evaporate. The ions get closer together as the droplets get smaller. As the ions get closer together, the repulsive charges increase to the point that the droplet explodes or the analyte ions evaporate from the small droplets.
