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Bottom-Up Low Molecular Weight Heparin Analysis Using Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive Characterization
[Image: see text] Low molecular weight heparins (LMWHs) are heterogeneous, polydisperse, and highly negatively charged mixtures of glycosaminoglycan chains prescribed as anticoagulants. The detailed characterization of LMWH is important for the drug quality assurance and for new drug research and de...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082394/ https://www.ncbi.nlm.nih.gov/pubmed/24905078 http://dx.doi.org/10.1021/ac501301v |
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author | Li, Guoyun Steppich, Julia Wang, Zhenyu Sun, Yi Xue, Changhu Linhardt, Robert J. Li, Lingyun |
author_facet | Li, Guoyun Steppich, Julia Wang, Zhenyu Sun, Yi Xue, Changhu Linhardt, Robert J. Li, Lingyun |
author_sort | Li, Guoyun |
collection | PubMed |
description | [Image: see text] Low molecular weight heparins (LMWHs) are heterogeneous, polydisperse, and highly negatively charged mixtures of glycosaminoglycan chains prescribed as anticoagulants. The detailed characterization of LMWH is important for the drug quality assurance and for new drug research and development. In this study, online hydrophilic interaction chromatography (HILIC) Fourier transform mass spectrometry (FTMS) was applied to analyze the oligosaccharide fragments of LMWHs generated by heparin lyase II digestion. More than 40 oligosaccharide fragments of LMWH were quantified and used to compare LMWHs prepared by three different manufacturers. The quantified fragment structures included unsaturated disaccharides/oligosaccharides arising from the prominent repeating units of these LMWHs, 3-O-sulfo containing tetrasaccharides arising from their antithrombin III binding sites, 1,6-anhydro ring-containing oligosaccharides formed during their manufacture, saturated uronic acid oligosaccharides coming from some chain nonreducing ends, and oxidized linkage region oligosaccharides coming from some chain reducing ends. This bottom-up approach provides rich detailed structural analysis and quantitative information with high accuracy and reproducibility. When combined with the top-down approach, HILIC LC-FTMS based analysis should be suitable for the advanced quality control and quality assurance in LMWH production. |
format | Online Article Text |
id | pubmed-4082394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-40823942015-06-06 Bottom-Up Low Molecular Weight Heparin Analysis Using Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive Characterization Li, Guoyun Steppich, Julia Wang, Zhenyu Sun, Yi Xue, Changhu Linhardt, Robert J. Li, Lingyun Anal Chem [Image: see text] Low molecular weight heparins (LMWHs) are heterogeneous, polydisperse, and highly negatively charged mixtures of glycosaminoglycan chains prescribed as anticoagulants. The detailed characterization of LMWH is important for the drug quality assurance and for new drug research and development. In this study, online hydrophilic interaction chromatography (HILIC) Fourier transform mass spectrometry (FTMS) was applied to analyze the oligosaccharide fragments of LMWHs generated by heparin lyase II digestion. More than 40 oligosaccharide fragments of LMWH were quantified and used to compare LMWHs prepared by three different manufacturers. The quantified fragment structures included unsaturated disaccharides/oligosaccharides arising from the prominent repeating units of these LMWHs, 3-O-sulfo containing tetrasaccharides arising from their antithrombin III binding sites, 1,6-anhydro ring-containing oligosaccharides formed during their manufacture, saturated uronic acid oligosaccharides coming from some chain nonreducing ends, and oxidized linkage region oligosaccharides coming from some chain reducing ends. This bottom-up approach provides rich detailed structural analysis and quantitative information with high accuracy and reproducibility. When combined with the top-down approach, HILIC LC-FTMS based analysis should be suitable for the advanced quality control and quality assurance in LMWH production. American Chemical Society 2014-06-06 2014-07-01 /pmc/articles/PMC4082394/ /pubmed/24905078 http://dx.doi.org/10.1021/ac501301v Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) |
spellingShingle | Li, Guoyun Steppich, Julia Wang, Zhenyu Sun, Yi Xue, Changhu Linhardt, Robert J. Li, Lingyun Bottom-Up Low Molecular Weight Heparin Analysis Using Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive Characterization |
title | Bottom-Up Low Molecular Weight Heparin Analysis Using
Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive
Characterization |
title_full | Bottom-Up Low Molecular Weight Heparin Analysis Using
Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive
Characterization |
title_fullStr | Bottom-Up Low Molecular Weight Heparin Analysis Using
Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive
Characterization |
title_full_unstemmed | Bottom-Up Low Molecular Weight Heparin Analysis Using
Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive
Characterization |
title_short | Bottom-Up Low Molecular Weight Heparin Analysis Using
Liquid Chromatography-Fourier Transform Mass Spectrometry for Extensive
Characterization |
title_sort | bottom-up low molecular weight heparin analysis using
liquid chromatography-fourier transform mass spectrometry for extensive
characterization |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082394/ https://www.ncbi.nlm.nih.gov/pubmed/24905078 http://dx.doi.org/10.1021/ac501301v |
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