A complex protein mixture is analyzed by jointly digesting the mixture, separating the digest peptides chromatographically or electrophoretically, and ionizing the digest peptides eluting from the separation device by an ionizing method that generates multiply charged ions. Digest peptide ions within a pre-selected range of m/z-values are isolated in an RF ion trap and subsequently reduced in their charge state. The charge-reduced ions can be measured with very high sensitivity. By repeating this process with adjacent isolation mass windows within the time duration of each separation peak, it is possible to determine the masses m, the prevalent charge states z, the retention times t, and the intensities i of a huge number of digest peptides of the complex protein mixture in a single separation run.