The effects of different experimental parameters on rate constant measurements performed by mass spectrometry were investigated with a two-level fractional factorial design. This chemometric technique allows a study of the effects of selected factors and of their interactions on the response of an experiment by performing a limited number of analyses. The selected factors were: sample pressure, energy of the ionising electrons, reaction time and ionisation time. In this work, two mass spectrometric techniques were compared: Fourier transform ion cyclotron resonance (FT-ICR) and quadrupole ion trap (QIT) mass spectrometries. Experimental results were obtained from a study of a reaction system consisting of the condensation between triethylphosphite and its fragment ion (CH(3)CH(2)O)(2)P(+). Apparent bimolecular rate constants are clearly larger when determined by QIT than by FT-ICR, because of collisional stabilisation of the adduct ion by helium buffer gas introduced in the QIT spectrometer. However, the QIT rate constant extrapolated to zero helium pressure is almost identical to the FT-ICR value; this supports the conclusion regarding the buffer gas effect. Minor effects evidenced by the chemometric method were attributed to the sample pressure and to the reaction time.