کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8513450 1556496 2018 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Use of a 2,2'-Azobis (2-Amidinopropane) Dihydrochloride Stress Model as an Indicator of Oxidation Susceptibility for Monoclonal Antibodies
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
The Use of a 2,2'-Azobis (2-Amidinopropane) Dihydrochloride Stress Model as an Indicator of Oxidation Susceptibility for Monoclonal Antibodies
چکیده انگلیسی
Protein oxidation is a major pathway for degradation of biologic drug products. Past literature reports have suggested that 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator that produces alkoxyl and alkyl peroxyl radicals, is a useful model reagent stress for assessing the oxidative susceptibility of proteins. Here, we expand the applications of the AAPH model by pairing it with a rapid peptide map method to enable site-specific studies of oxidative susceptibility of monoclonal antibodies and their derivatives for comparison between formats, the evaluation of formulation components, and comparisons across the stress models. Comparing the free radical-induced oxidation model by AAPH with a light-induced oxidation model suggests that light-sensitive residues represent a subset of AAPH-sensitive residues and therefore AAPH can be used as a preliminary screen to highlight molecules that need further assessment by light models. In sum, these studies demonstrate that AAPH stress can be used in multiple ways to evaluate labile residues and oxidation sensitivity as it pertains to developability and manufacturability.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 2, February 2018, Pages 550-558
نویسندگان
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