KB002037: What do Negative Peaks in the Mass Spec Chromatogram Indicate? - General LC/MS 

Negative peaks in the mass spec chromatogram (either TIC or EIC) generally result when compound(s) with a higher proton affinity co-elute(s) with the compound of interest. If you are acquiring data in SIM mode, run the method in scan mode with a mass range of 100 to 400 amu to determine what is coeluting with the compound of interest. It will be necessary to eliminate this interference in order to prevent the ion for the compound of interest from being suppressed. It may be possible to separate the compounds with chromatography using a gradient method and/or different mobile phase components (i.e. acetonitrile rather than MeOH)