The amine-reactive, NHS-ester-activated compounds covalently attach to the peptide amino terminus and free amino termini of lysine residues of peptides and proteins with high efficiency, thereby labeling all peptides in each sample regardless of enzyme used for digestion. Since TMT reagents share an identical structure and mass (i.e., isotopomers), labeled peptides co-elute during LC separation and are co-isolated during MS/MS analysis, resulting in fewer missing peptide identifications among samples. During MS/MS analysis, each isobaric tag is also fragmented to produce a unique reporter ion mass that is used for sample identification and quantitation. Protein quantitation is accomplished by comparing the relative intensities of the two reporter ions in the MS/MS spectra.