کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8514732 | 1556511 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rapid Conformational Analysis of Protein Drugs in Formulation by Hydrogen/Deuterium Exchange Mass Spectrometry
ترجمه فارسی عنوان
تجزیه و تحلیل متقابل سریع مواد مخدر در پروتئین در فرمولاسیون اسپکترومتر جرم مبادله هیدروژن / دئتریوم
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
LC-MSAnalytical biochemistry - بیوشیمی تحلیلیPhysical stability - ثبات فیزیکیbiopharmaceuticals characterization - خصوصیات بیوفارمینتیکProtein structure - ساختار پروتئینAnalytical chemistry - شیمی تجزیهMass spectrometry - طیف سنجی جرمیProtein formulation - فرمول پروتئینFormulation - فرمولاسیونprotein folding/refolding - پروتئین تاشو / انجماد
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
Hydrogen deuterium exchange coupled to mass spectrometry (HDX-MS) has become an established method for analysis of protein higher order structure. Here, we use HDX-MS methodology based on manual solid-phase extraction (SPE) to allow fast and simplified conformational analysis of proteins under pharmaceutically relevant formulation conditions. Of significant practical utility, the methodology allows global HDX-MS analyses to be performed without refrigeration or external cooling of the setup. In mode 1, we used dimethyl sulphoxide-containing solvents for SPE, allowing the HDX-MS analysis to be performed at acceptable back-exchange levels (<30%) without the need for cooling any components of the setup. In mode 2, SPE and chromatography were performed using fast isocratic elution at 0°C resulting in a back-exchange of 10%-30%. Real-world applicability was demonstrated by HDX-MS analyses of interferon-β-1a in formulation, using an internal HDX reference peptide (P7I) to control for any sample-to-sample variations in back-exchange. Advantages of the methodology include low sample use, optimized excipient removal using multiple solvents, and fast data acquisition. Our results indicate that HDX-MS can provide a reliable approach for fast conformation analysis of proteins in their intended formulations, which could facilitate an increased use of the technique in pharmaceutical development research.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 11, November 2016, Pages 3269-3277
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 11, November 2016, Pages 3269-3277
نویسندگان
Zeinab E. Nazari, Marco van de Weert, George Bou-Assaf, Damian Houde, Andrew Weiskopf, Kasper D. Rand,