Charge Detection FT-ICR Mass Spectrometry: From Direct Mass Determination to Profiling Gas-Phase Reaction Events

Charge Detection Mass Spectrometry is a powerful method for characterizing the mass distribution of ultraheterogeneous biopolymers that relies on the detection of individual ion signals. Here, we show that Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) enables routine measurement of individual ion signals, thereby facilitating charge-detection analysis for both native and denatured proteins. The capabilities of FT-ICR MS to measure seconds-long transients from single ions afford a unique opportunity to observe multiple gas-phase interconversions with temporal resolution. Collectively, these findings indicate that FT-ICR MS is well-suited for probing the gas-phase behavior of large ions, enabling precise measurements of charge, mass, and ion stability at the individual-ion level.