Glycosylation-based distinction of endogenous and recombinant complement factor H enables selective quantification in human plasma

Generally, a high degree of structural similarity between endogenous and therapeutic proteins is essential. From a pharmacokinetic perspective, however, it is advantageous to selectively quantify the exogenous protein.</p> <p>This study presents a strategy for the specific quantification of CPV 104, a recombinant form of complement factor H (FH), in human plasma.

Because CPV 104 is identical in amino acid sequence to endogenous FH, differential HPLC-MS/MS analysis was used to identify structural features that discriminate both forms.</p> <p>Differential analysis revealed unique glycosylation patterns on CPV 104, enabling development of a targeted HPLC-MS/MS assay for CPV 104-specific glycopeptides. Assay robustness was further enhanced by incorporating CPV 104 with stable isotope labeled glycan residues as an internal standard.