Triple Resonance Methods to Improve Performance of Ion Trap Precursor and Neutral Loss Scans.

Two experiments are described that extend the capabilities of quadrupole ion trap mass spectrometers operated in the precursor and neutral loss scan mode. The first experiment, a triple resonance precursor ion scan, is used to enhance sensitivity, selectivity, and molecular coverage. This method augments the ion trap precursor ion scan with the application of a second excitation frequency to selectively activate first-generation (MS2) product ions as they are formed and produce second-generation (MS3) product ions, which are then mass-selectively ejected with a third auxiliary signal and detected. This single mass analyzer experiment can be equated to performing the sequential precursor ion scan in a multiple analyzer system (Anal. Chem. 1990, 62 (17), 1809-1818). The second capability demonstrated is "frequency tagging", a method used to differentiate between ions ejected due to inherent instability under given trapping conditions, which causes artifacts during these scans, and ions that are resonantly ejected by the product ion ejection frequency. Beat frequencies are used to modulate resonance ejection peaks but conveniently do not modulate boundary ejection peaks. Frequency tagging provides a mechanism to identify the artifact peaks that are a consequence of operating at a high trapping voltage (i.e., low mass cutoff) for optimal precursor/product ion selectivity. The experiment is demonstrated for precursor and for neutral loss scans.