کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7626642 | 1494581 | 2018 | 26 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of product-related low molecular weight impurities in therapeutic monoclonal antibodies using hydrophilic interaction chromatography coupled with mass spectrometry
ترجمه فارسی عنوان
خصوصیات ناخالصی های کم مولکولی مربوط به محصول در آنتی بادی های مونوکلونال درمانی با استفاده از کروماتوگرافی تعامل هیدرولیکی و همراه با طیف سنجی جرمی
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی
Traditional SDS-PAGE method and its modern equivalent CE-SDS method are both widely applied to assess the purity of therapeutic monoclonal antibody (mAb) drug products. However, structural identification of low molecular weight (LMW) impurities using those methods has been challenging and largely based on empirical knowledges. In this paper, we present that hydrophilic interaction chromatography (HILIC) coupled with mass spectrometry analysis is a novel and orthogonal method to characterize such LMW impurities present within a purified mAb drug product sample. We show here that after removal of N-linked glycans, the HILIC method separates mAb-related LMW impurities with a size-based elution order. The subsequent mass measurement from a high-resolution accurate mass spectrometer provides direct and unambiguous identification of a variety of low-abundance LMW impurities within a single LC-MS analysis. Free light chain, half antibody, H2L species (antibody possessing a single light chain) and protein backbone-truncated species can all be confidently identified and elucidated in great detail, including the truncation sites and associated post-translational modifications. It is worth noting that this study provides the first example where the H2L species can be directly detected in a mAb drug product sample by intact mass analysis without prior enrichment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 154, 30 May 2018, Pages 468-475
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 154, 30 May 2018, Pages 468-475
نویسندگان
Shunhai Wang, Anita P. Liu, Yuetian Yan, Thomas J. Daly, Ning Li,