A method of checking or adjusting the calibration of a mass spectrometer is disclosed. The method comprises fragmenting parent or precursor ions and generating fragment or product ion mass spectral data and recognizing first neutral loss ions in the fragment or product ion mass spectral data. The method further comprises determining a first mass loss difference between the parent or precursor ions and the first neutral loss ions and determining whether the first mass loss difference corresponds with an expected or pre-determined mass loss difference, wherein if it is determined that the first mass loss difference does not correspond with an expected or pre-determined mass loss difference then the method further comprises adjusting one or more calibration parameters.