Precursor Resolution via Ion Z-State Manipulation: A Tandem Mass Spectrometry Approach for the Analysis of Mixtures of Multiply-Charged Ions

Electrospray ionization (ESI) is often the ionization method of choice, particularly for high-mass polar molecules and complexes. However, when analyzing mixtures of analytes, charge state ambiguities and overlap in mass-to-charge (m/z) can arise from species with different masses and charges. While solution-phase conditions can sometimes be optimized to produce relatively low charge states—thereby reducing charge-state ambiguity and m/z overlap—gas-phase methods offer greater control over charge state reduction. For complex mixtures, however, charge state reduction alone often fails to resolve individual components in the mixture. Incorporating a mass-selection step prior to charge state manipulation can simplify the mixture and significantly improve the separation of the components. This general tandem mass spectrometry approach is referred to here as precursor resolution via ion z-state manipulation (PRIZM). Examples of variations of PRIZM experiments date back roughly 25 years and have involved ion/molecule proton transfer reactions, ion/ion proton transfer reactions, ion/ion electron transfer reactions, electron capture reactions, and multiply-charged ion attachment reactions. This tutorial review describes the PRIZM approach and provides illustrative examples using each of the charge state manipulation approaches mentioned above.