Biomolecules such as proteins and nucleic acids are low volatility compounds with high molecular weights. Conventional electron-impact ionization mass spectrometry faces challenges with such molecules, including severe molecular fragmentation.

Electrospray ionization is an alternative "soft" ionization method that generates nonradical molecular ions for the mass spectrometry of such biomolecules.

In this method, the sample is mixed with a polar solvent such as methanol, methanol-water, or acetonitrile with or without added salts.

The mixture is sprayed via a high voltage capillary into a vacuum chamber. The rapid evaporation of solvent from the fine spray of charged droplets ultimately leads to the charged gaseous sample molecule.

This charged sample molecule is detected in the mass spectrum as the sum of the sample molecular mass and the masses of the associated ions.

For example, if sodium ions are present in the ionic solution, the spectrum typically features an M+23 peak.