We present basic work-ups and quantitative comparisons for two current generation Orbitrap mass spectrometers, the Q Exactive Plus and Orbitrap Fusion Tribrid, that are widely considered two of the highest performing instruments on the market. We assessed the performance of two quantitative methods on both instruments, namely label free quantitation and stable isotope labelling using isobaric tags, for studying the heat shock response in Escherichia coli. We investigated the recently reported MS3 method on the Fusion instrument and the potential of MS3 based reporter ion isolation Synchronous Precursor Selection (SPS) and its impact on quantitative accuracy. We confirm that the label free approach offers a more linear response with a wider dynamic range than MS2 based isobaric tag quantitation and that the MS3/SPS approach alleviates but does not eliminate dynamic range compression. We observed, however, that the choice of quantitative approach had little impact on the ability to statistically evaluate the E.coli heat shock response. We conclude that in the experimental conditions tested, MS2 based reporter ion quantitation provides reliable biological insight despite the issue of compressed dynamic range, an observation which significantly impacts the choice of instrument. This article is protected by copyright. All rights reserved