The invention provides reagents and methods for the accurate quantification of proteins in complex biological samples. Quantification is obtained by adding to a sample a peptide combo which is essentially a collection of synthetic reference peptides. Said synthetic reference peptides have a small mass difference when compared to the biological reference peptides that originate upon digestion from the proteins present in the sample. Reference peptides a nd synthetic reference peptides are selected and the identity and accurate amounts of reference peptides are determined by mass spectrometry. The metho ds can be used in high throughput assays to interrogate proteomes.
