title: Qualitative and quantitative assessment of marketed erythropoiesis-stimulating agents by capillary electrophoresis.
abstract: Formulated erythropoiesis stimulating agents (ESAs) containing erythropoietin (EPO)-alpha, EPO-beta or darbepoetin-alpha were analyzed by capillary electrophoresis with a previously published method requiring no sample pre-treatment [1]. In this study, the method proved to be applicable to all formulations encountered, that is, in the presence of polysorbate 80, polysorbate 20 or human serum albumin as major excipients, thus extending the range of products that can be analyzed without pre-treatment. Method performance was evaluated and showed good linearity, range, precision and sensitivity. No significant matrix effects were observed for the various formulations. The ability of the method to resolve isoforms of each of the three active ingredients enabled comparison of the isoform distribution of finished products with that of the respective drug substance. In general, finished products and their corresponding drug substances showed similar isoform distribution and all were within manufacturer specifications. In addition, the content in active ingredient in the various dosage strengths was found to be in close agreement with the label claims with the exception of 2 out of 131 containers analyzed. Overall, this study demonstrated that the capillary zone electrophoresis method could be successfully applied to the analysis of most of the ESA products currently on the market in North America and Europe and that all products were found to have good batch-to-batch consistency.
authors.affiliation: Biologics and Genetic Therapies Directorate, Health Canada, 251- Sir Frederick Banting Driveway, Ottawa, ON K1A 0K9, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Boucher
authors.forename: Anita
authors.initials: A
authors.lastname: Kane
authors.forename: Michel
authors.initials: M
authors.lastname: Girard
mesh_terms: D000068256:Darbepoetin alfa; D019075:Electrophoresis, Capillary / Q000379:methods*; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D006397:Hematinics / Q000737:chemistry*; D006801:Humans; D011136:Polysorbates / Q000737:chemistry; D020033:Protein Isoforms; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D005079:Excipients; D006397:Hematinics; D011136:Polysorbates; D020033:Protein Isoforms; D012709:Serum Albumin; D004921:Erythropoietin; D000068256:Darbepoetin alfa