Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies
| Autor: | Guillaume Chevreux, Zera Tellier, M.-H. Andre, M. Jube, Y. Leblanc, Nicolas Bihoreau |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
IVIg Glycosylation Chemistry Pharmaceutical Carbohydrates Pharmaceutical Science 01 natural sciences Excipients 03 medical and health sciences symbols.namesake chemistry.chemical_compound Drug Stability Glycation Tandem Mass Spectrometry Protein formulation Immunoglobulin Sugar chemistry.chemical_classification Chromatography biology Mass spectrometry 010401 analytical chemistry Immunoglobulin Fc Fragments Temperature Immunoglobulins Intravenous General Medicine Maltose 0104 chemical sciences Reducing sugar Maillard reaction 030104 developmental biology Glucose chemistry Biochemistry Polyclonal antibodies Immunoglobulin G symbols biology.protein Chromatography Liquid Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 102:185-190 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2016.03.016 |
| Popis: | A number of intravenous immunoglobulin preparations are stabilized with sugar additives that may lead over time to undesirable glycation reactions especially in liquid formulation. This study aimed to evaluate the reactivity of sugar excipients on such preparations in condition of temperature, formulation and concentration commonly used for pharmaceutical products. Through an innovative LC-MS method reported to characterize post-translational modifications of IgGs Fc/2 fragments, a stability study of IVIg formulated with reducing and non-reducing sugars has been undertaken. The rate of polyclonal IgGs glycation was investigated during 6months at 5, 25, 30 and 40°C. High levels of glycation were observed with reducing sugars such as glucose and maltose in the first months of the stability study from 25°C. Non-reducing sugars presented a low reactivity even at the highest tested temperature (40°C). Furthermore, a site by site analysis was performed by MS/MS to determine the glycation sites which were mainly identified at Lys246, Lys248 and Lys324. This work points out the high probability of glycation reactions in some commercialized products and describes a useful method to characterize IVIg glycated products issued from reducing sugar excipients. |
| Databáze: | OpenAIRE |
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