Two-Dimensional Correlation Mass Spectrometry for Precursor/Fragment Ion Identification of Composite and Unresolved Spectral Peaks

Two-dimensional correlation mass spectrometry (2D-CMS) is a cross-correlation-based technique that can be used to identify mass-spectral signals that arise from a common molecular origin. In this study, 2D-CMS is explored for mixtures of the blood-pressure medications atenolol and metoprolol with the specific aims of precursor/fragment-ion identification and deconvolution of unresolved spectral peaks. Atenolol and metoprolol are structurally similar and produce several identical or isobaric fragment ions. In addition, the first isotopic peak of the atenolol ion (i.e., [MH++1]) at m/z 268.1737 and the protonated metoprolol ion at m/z 268.1834 produce an isobaric overlap for the mass-spectral resolving power used in this study (m/Δm = 17,500 at m/z 200). These phenomena result in numerous peaks that originate from both analytes, complicating the interpretation of mass-spectral results for precursor/fragment identification and assignment of overlapped peaks. Semiquantitative information extracted from 2D-CMS results enabled the determination of the relative contribution of each analyte to the total signal of their shared fragments. In addition, narrow m/z regions within unresolved mass-spectral peaks could be attributed to their specific molecular origin. For a series of solutions with varying proportions of each analyte, metrics derived from 2D-CMS were found to scale with the relative concentration of each analyte. Calibration results obtained from 2D-CMS were comparable to those obtained from traditional peak-fitting methods but provided additional information that enabled peak identification. These results show the utility of 2D-CMS for deconvolution of mass spectra acquired without separation or isolation of analytes or at low resolving powers.