Charge manipulation for improved mass determination of high-mass species and mixture components by electrospray mass spectrometry

The manipulation of the charge states of high‐mass ions can facilitate mass determination in electrospray (ES) mass spectrometry. Specifically, the reduction of charge (which leads to ions of higher mass‐to‐charge ratios) can significantly reduce peak overlap. Signals associated with various charge states of high‐mass ions are more easily resolved at low charge states and chemical noise tends to be significantly lower at high mass‐to‐charge ratios than in the normal mass‐to‐charge window typically associated with electrospray. Algorithms that transform ES mass spectra to zero‐charge spectra are most likely to yield unambiguous results when charge states are clearly resolved and when signal‐to‐noise ratios are relatively high. Charge manipulation can enhance the value of the transformation algorithms in cases in which compromises their utility. Such situations include ES mass spectra of high‐mass species that yield charge states that are not baseline resolved, mixtures with many components and mixtures in which the signals from major components overwhelm signals from minor components. Examples of improved mass determination are illustrated for proteins using ion–ion chemistry as the means for charge state manipulation and the quadrupole ion trap as the mass analyzer. © 1998 John Wiley & Sons, Ltd.