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

Li, G.
Steppich, J.
Wang, Z.
Sun, Y.
Xue, C.
Linhardt, Robert J.
Li, L.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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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.
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.
Analytical Chemistry, 86, 6626−6632
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
American Chemical Society (ACS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
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