LC/MS instruments use a variety of ionization techniques, collectively called atmospheric pressure ionization (API). Detectors of this type can detect positive or negative ions.

API techniques offer soft ionization, usually with little or no fragmentation. An API spectrum typically contains peaks for only the protonated or deprotonated molecule. Compounds with basic sites (such as amines) can form protonated molecules (that is, [M+H]+, where M represents the monoisotopic molecular weight of the neutral compound). In the positive-ion detection mode (polarity +), these ions produce a spectrum peak at the m/z value M+1.

Compounds with acidic sites (for example, sulfonic acids) can form deprotonated molecules, [M–H]–. In the negative-ion detection mode (polarity –), these ions produce a spectrum peak at the m/z value M–1.