For pyrolysis mass spectrometry (PyMS) to be used for the routine identification of microorganisms, for quantifying determinands in biological and biotechnological systems, and in the production of useful mass spectral libraries, it is paramount that newly acquired spectra be compared to those previously collected. Neural network and other multivariate calibration models have been used to relate mass spectra to the biological features of interest. As commonly observed, however, mass spectral fingerprints showed a lack of long-term reproducibility, due to instrumental drift in the mass spectrometer; when identical materials were analyzed by PyMS at dates from 4 to 20 months apart, neural network models produced at earlier times could not be used to give accurate estimates of determinand concentrations or bacterial identities. Neural networks, however, can be used to correct for pyrolysis mass spectrometer instrumental drift itself, so that neural network or other multivariate calibration models created using previously collected data can be used to give accurate estimates of determinand concentration or the nature of bacteria (or, indeed, other materials) from newly acquired pyrolysis mass spectra. This approach is not limited solely to pyrolysis mass spectrometry but is generally applicable to any analytical tool which is prone to instrumental drift, such as IR, ESR, NMR and other spectroscopies, and gas and liquid chromatography, as well as other types of mass spectrometry.