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Covalent modification can (negatively) affect the ionization of peptide fragments, and it is not uncommon to only detect unmodified fragment ions (Figure 5B) [82,84,88]: LC-MS/MS analysis of the trypsin- and GluC-digested covalent adduct confirmed covalent binding of tirabrutinib (ONO-4059) [88] to the BTK Y476–R487 precursor peptide (MS1), but only unmodified fragment ions and fragmentation of the parent inhibitor were found in MS2

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Medicare policies are established by the Centers for Medicare and Medicaid Services, but implementation is handled by Medicare Administrative Contractors through Local Coverage Determinations