Determining the elemental compositions of unknown molecules is an important goal of analytical chemistry. The isotope pattern revealed by a mass spectrometer provides valuable information regarding the elemental composition of a molecule. In order to employ spectral accuracy considerations for elemental composition determination, it is important to know how faithfully a mass spectrometer can record the isotope pattern and to understand the magnitude of the errors of the relative isotopic abundances.
Twenty‐four small molecule drugs and two natural products representing a diverse range of elemental compositions and ranging in molecular weight from 236 to 1663 Da were measured on a new hybrid orthogonal acceleration quadrupole time‐of‐flight (Q‐TOF) mass spectrometer by flow infusion analysis. The similarity between the observed profile isotope pattern and the theoretical isotope pattern, denoted spectral accuracy, was calculated using a computational algorithm in the program MassWorks.
The spectral accuracy for all compounds averaged better than 98%. When using spectral accuracy to rank elemental compositions with the elemental constraints (C1–100H0–200N0–50O0–50F0–5S0–5Cl0–5Br0–5) further restricted by empirical rules and a mass tolerance ≤5 parts‐per‐million, the correct formula was ranked first over 80% of the time. In contrast, when using mass accuracy for ranking, only two compounds (8%) were ranked first. For quinidine and troglitazone, the initial spectral accuracy measurements were lower than expected and further analysis indicated that minor, structurally related components were present.
Our work has determined the magnitude of spectral accuracy that can be expected on a new Q‐TOF mass spectrometer. In addition, we demonstrate the utility of spectral accuracy measurements both for ranking elemental compositions and also for obtaining insight into the chemical nature of the analyte that might otherwise be overlooked. Copyright © 2012 John Wiley & Sons, Ltd.