MS Platform for Erythropoietin Glycome Characterization

Abstract

Recombinant erythropoietins (EPOs) are an important class of biotherapeutics that stimulate red blood cell produc- tion. The quality, safety, and potency of EPO variants are determined largely by their glycosylation, which makes up nearly half their mass. Thus, detailed glycomic analyses are important to assess biotherapeutic quality and establish the equivalency of bio- similar EPOs now coming to market. High-resolution mass spectrometry (MS) has recently emerged as the premier tool for gly- can analysis in EPOs. Using the accurate mass measurements provided by high-resolution MS, the compositions of even large, complex glycans can easily be determined. When combined with a nano-LC separation, differentiation of structural isomers also becomes a possibility. These components, together, provide a comprehensive picture of biotherapeutic glycosylation. In this review, we provide an overview of MS-based analytical platform for glycomic characterization of EPO biotherapeutics and bio- similars.