a) providing a sample containing the target biomolecule, wherein the target biomolecule comprises a polypeptide having a region modified by a post-translational modification (PTM);

b) reacting the target biomolecule with a tagging reagent to generate a labeled biomolecule, wherein the reacting step comprises adding the tagging reagent with 2,3-butanedione, 2,3-butanedione monoxime, or a phenylglyoxal derivative to the target biomolecule thereby generating a derivatized polypeptide from the polypeptide having the region modified by the PTM, wherein the tagging reagent comprises a thiol group or a disulfide group able to react with the derivatized polypeptide, and wherein reacting the tagging reagent with the target biomolecule imparts a mass shift to the target biomolecule;

c) ionizing the labeled biomolecule to form a precursor ion;

d) detecting and analyzing the precursor ion using a mass spectrometer; and

e) identifying biomolecules with mass spectrometry data;

wherein the phenylglyoxal derivative has the formula:

where R₁ comprises a thiol group or is functional group able to react with a biotin-thiol tag.