کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5130989 1490871 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR
چکیده انگلیسی


- Low molecular weight heparins prepared from different heparin parents were analyzed.
- An integrated analytical approach relied on LC-MS and NMR analysis.
- Monosaccharide compositional analysis relied on top-down NMR analysis.
- Intact chain, oligosaccharide, and disaccharide analyses relied on LC-MS.
- Differences due to parent heparin were observed using principal component analysis.

Heparin is a structurally complex, polysaccharide anticoagulant derived from livestock, primarily porcine intestinal tissues. Low molecular weight (LMW) heparins are derived through the controlled partial depolymerization of heparin. Increased manufacturing and regulatory concerns have provided the motivation for the development of more sophisticated analytical methods for determining both their structure and pedigree. A strategy, for the comprehensive comparison of parent heparins and their LMW heparin daughters, is described that relies on the analysis of monosaccharide composition, disaccharide composition, and oligosaccharide composition. Liquid chromatography-mass spectrometry is rapid, robust, and amenable to automated processing and interpretation of both top-down and bottom-up analyses. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues and glucosamine substitution. Principal component analysis (PCA) was applied to the normalized abundance of oligosaccharides, calculated in the bottom-up analysis, to show parent and daughter correlation in oligosaccharide composition. Using these approaches, six pairs of parent heparins and their daughter generic enoxaparins from two different manufacturers were comprehensively analyzed. Enoxaparin is the most widely used LMW heparin and is prepared through controlled chemical β-eliminative cleavage of porcine intestinal heparin. Lovenox®, the innovator version of enoxaparin marketed in the US, was analyzed as a reference for the daughter LMW heparins. The results, show similarities between LMW heparins from two different manufacturers with Lovenox®, excellent lot-to-lot consistency of products from each manufacturer, and detects a correlation between each parent heparin and daughter LMW heparin.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Analytica Chimica Acta - Volume 961, 8 April 2017, Pages 91-99
نویسندگان
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