Characterization of Methionine Oxidation In a Parathyroid Hormone Formulation Using LC/TOF MS and LC/MS/MS

摘要

Using high resolution and tandem mass spectrometers in conjunction with CNBr digestion, all anticipated digested peptides, including both oxidized and non-oxidized fragments, were positively identified for methionine sulfoxide formation at positions 8 and 18. TOF MS capability facilitated the observation of multiple charge states and the clear mass assignments of the peptide fragments without the need of further enzymatic digestion. Additional LC/MS~(n) studies confirmed the characteristic neutral loss of sulfinic acid resulting from methionine sulfoxide formation. The neutral losses detected in the MS/MS/MS process are unique to the charge status of the parent peptide ions. Three identified oxidation products, PTH Met8(O)Met18(O), PTH Met8(O), and PTH Met18O, were injected onto the original non-MS compatible HPLC method and their peak retention times were confirmed.