Comparisons of samples of proteins. Methods are provided for detecting quantitative and / or quantitatively the presence of mutations, modifications or impurities in a sample of protein.The methods use variants of isotope labelled amino acids incorporadoas in proteins prior to the digestion of protein, so as to enable comparisons of two samples of protein in liquid chromatography using bottom-up.The measurements obtained by the present invention take into consideration not only the masses of the peptides generated during proteolytic digestion, but also the abundance of each resulting peptide. The measurement of the abundance of peptides by MS is allowed through the use of a sitrs sample which is mixed with a protein non scheduled prior to the digestion of proteins.As used here, the term "sample sitrs" or "standard sitrs" means a protein (for example, an antibody) of known sequence, labeled with a stable isotope marked variation in at least one amino acid present in the protein.
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