Achieving high mass accuracy is of great importance in LC/MS applications for the identification of metabolites in pharmaceutical industries, key bio-chemicals in environmental monitoring, and hazardous materials in the homeland defense area. High mass accuracy has typically been achieved through higher resolution mass spectrometers such as the triple stage quadrupole MS, qTOF, TOF or even FT-MS, which come at higher costs and larger instrument footprints.

This paper will provide a careful and fresh look at the many factors of importance to high mass accuracy including signal-to-noise, resolution, peak shapes, detector characteristics, sampling rate in order to point out the deficiencies on commercial systems. A fundamentally novel and different approach will be proposed for mass spectral data processing that will insure high mass accuracy as well as unbiased quantitative results for qualitative analysis such as metabolite identification and peptide mapping.

This new approach to mass spectral analysis will be demonstrated on conventional quadrupole MS systems as well as high resolution qTOF MS systems coupled with LC separation for the identification of metabolites from microsome incubation of Buspirone.