title: Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies.
abstract: 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.
authors.affiliation: LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtabœuf (Les Ulis), France.
authors.forename: Y
authors.initials: Y
authors.lastname: Leblanc
authors.affiliation: LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtabœuf (Les Ulis), France.
authors.forename: N
authors.initials: N
authors.lastname: Bihoreau
authors.affiliation: LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtabœuf (Les Ulis), France.
authors.forename: M
authors.initials: M
authors.lastname: Jube
authors.affiliation: LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtabœuf (Les Ulis), France.
authors.forename: M-H
authors.initials: MH
authors.lastname: Andre
authors.affiliation: LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtabœuf (Les Ulis), France.
authors.forename: Z
authors.initials: Z
authors.lastname: Tellier
authors.affiliation: LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtabœuf (Les Ulis), France. Electronic address: chevreuxg@lfb.fr.
authors.forename: G
authors.initials: G
authors.lastname: Chevreux
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D006031:Glycosylation; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry*; D016756:Immunoglobulins, Intravenous / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods; D013696:Temperature
chemical_list: D002241:Carbohydrates; D005079:Excipients; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D005947:Glucose
keywords: Excipients; Glycation; IVIg; Immunoglobulin; Maillard reaction; Mass spectrometry; Protein formulation