کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7612241 1493555 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Analysis of free drug fractions by ultrafast affinity extraction: Interactions of sulfonylurea drugs with normal or glycated human serum albumin
ترجمه فارسی عنوان
تجزیه و تحلیل فرآورده های مواد مخدر آزاد با استفاده از استخراج فوق العاده بالفعل: تعاملات داروهای سولفونیل اوره با آلبومین سرم انسانی طبیعی یا گلیکوزی
کلمات کلیدی
استخراج فوق العاده تراکم، کروماتوگرافی وابستگی، پیوند پروتئینی دارو، داروهای سولفونیل اوره، آلبومین سرم انسان، گلیسیری پروتئین،
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی
Ultrafast affinity extraction and a multi-dimensional affinity system were developed for measuring free drug fractions at therapeutic levels. This approach was used to compare the free fractions and global affinity constants of several sulfonylurea drugs in the presence of normal human serum albumin (HSA) or glycated forms of this protein, as are produced during diabetes. Affinity microcolumns containing immobilized HSA were first used to extract the free drug fractions in injected drug/protein mixtures. As the retained drug eluted from the HSA microcolumn, it was passed through a second HSA column for further separation and measurement. Items that were considered during the optimization of this approach included the column sizes and flow rates that were used, and the time at which the second column was placed on-line with the HSA microcolumn. This method required only 1.0 μL of a sample per injection and was able to measure free drug fractions as small as 0.09-2.58% with an absolute precision of ±0.02-0.5%. The results that were obtained indicated that glycation can affect the free fractions of sulfonylurea drugs at typical therapeutic levels and that the size of this effect varies with the level of HSA glycation. Global affinity constants that were estimated from these free drug fractions gave good agreement with those predicted from previous binding studies or determined through a reference method. The same approach could be utilized with other drugs and proteins or modified binding agents of clinical or pharmaceutical interest.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1371, 5 December 2014, Pages 82-89
نویسندگان
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