Compositions and methods that allow for the rapid detection and accurate quantification of any polypeptides of interest are provided. Compositions include isolated polypeptides comprising at least one universal peptide tag, as well as isolated polynucleotides encoding such polypeptides. The universal peptide tags can be quantified by methods including, but not limited to, mass spectrometry, and can act as surrogates for determining the concentration of the polypeptides comprising the universal peptide tags. Methods provide for the detection and/or quantification of any polypeptides of interest that comprise at least one universal peptide tag, including methods using mass spectroscopy techniques. Methods are also provided for producing hosts, or cells or parts thereof, that comprise polypeptides comprising at least one universal peptide tag. Hosts, or cells, or parts thereof, include mammalian, bacterial, insect, yeast, viral or plant.