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    Bottom-up LMWH analysis using LC-FTMS for extensive characterization

    Author
    Li, G.; Steppich, J.; Wang, Z.; Sun, Y.; Xue, C.; Linhardt, Robert J.; Li, L.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    BOTTOM-UP LOW MOLECULAR WEIGHT HEPARIN ANALYSIS USING LIQUID.pdf (1.563Mb)
    Other Contributors
    Date Issued
    2014
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Bottom-up LMWH analysis using LC-FTMS for extensive characterization, G. Li, J. Steppich, Z. Wang, Y. Sun, C. Xue, R. J. Linhardt, L. Li, Analytical Chemistry, 86, 6626−6632, 2014.
    Metadata
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    URI
    https://hdl.handle.net/20.500.13015/5319; https://doi.org/10.1021/ac501301v
    Abstract
    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.;
    Description
    Analytical Chemistry, 86, 6626−6632; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    American Chemical Society (ACS)
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; https://harc.rpi.edu/;
    Access
    ACS AuthorChoice License; A full text version is available in DSpace@RPI;
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