Profiling Analysis of Low Molecular Weight Heparins by Multiple Heart-Cutting Two Dimensional Chromatography with Quadruple Time-of-Flight Mass Spectrometry

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Authors
Ouyang, Yilan
Zeng, Yangyang
Rong, Yinxiu
Song, Yue
Shi, Lv
Chen, Bo
Yang, Xinlei
Xu, Naiyu
Linhardt, Robert J.
Zhang, Zhenqing
Issue Date
2015-09-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.
Description
Analytical Chemistry, 87, 8957−8963
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Full Citation
Profiling Analysis of Low Molecular Weight Heparins by Multiple Heart-Cutting Two Dimensional Chromatography with Quadruple Time-of-Flight Mass Spectrometry, Y. Ouyang, Y. Zeng, Y. Rong, Y. Song, L. Shi, N. Xu, R. J. Linhardt, Z. Zhang, Analytical Chemistry, 87, 8957−8963, 2015.
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15206882
32700
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