n this work we utilize a standard, high-complexity Human cell line tryptic digest combined with a synthetic peptide library to systematically evaluate the properties of a variety of MS operation modes and detector configurations for the optimal examination of isobaric-tagged peptide mixtures. We demonstrate that despite the ability of the IT to yield more rapid MS3 scanning, the benefit in peptide and protein identifications when examining complex mixtures is minor while the negative impact on quantification precision is significant.