Development of hydrophilic interaction chromatography with quadruple-time-of-flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis
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Authors
Ouyang, Yilan
Wu, Chengling
Sun, Xue
Liu, Jianfen
Linhardt, Robert J.
Zhang, Zhenqing
Issue Date
2016-01-30
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Rationale: Heparin and low molecular weight heparin (LMWH) are widely used as clinical anticoagulants. The determination of their composition and structural heterogeneity still challenges analysts. Methods: Disaccharide compositional analysis, utilizing heparinase-catalyzed depolymerization, is one of the most important ways to evaluate the sequence, structural composition and quality of heparin and LMWH. Hydrophilic interaction chromatography coupled with quadruple time-of-flight mass spectrometry (HILIC/QTOFMS) has been developed to analyze the resulting digestion products. Results: HILIC shows good resolution and excellent MS compatibility. Digestion products of heparin and LMWHs afforded up to 16 compounds that were separated using HILIC and analyzed semi-quantitatively. These included eight common disaccharides, two disaccharides derived from chain termini, three 3-O-sulfo-group-containing tetrasaccharides, along with three linkage region tetrasaccharides and their derivatives. Structures of these digestion products were confirmed by mass spectral analysis. The disaccharide compositions of a heparin, two batches of the LMWH, enoxaparin, and two batches of the LMWH, nadroparin, were compared. In addition to identifying disaccharides, 3-O-sulfo-group-containing tetrasaccharides, linkage region tetrasaccharides were observed having slightly different compositions and contents in these heparin products suggesting that they had been prepared using different starting materials or production processes. Conclusions: Thus, compositional analysis using HILIC/QTOFMS offers a unique insight into different heparin products.
Description
Rapid Communications in Mass Spectrometry, 30, 277-284
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.
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.
Full Citation
Development of hydrophilic interaction chromatography with quadruple-time-of-flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis, C. Wu, Y. Ouyang, X. Sun, N. Xu, R. J. Linhardt, Z. Zhang, Rapid Communications in Mass Spectrometry, 30, 277-284, 2015.
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Volume
Issue
PubMed ID
DOI
ISSN
10970231
9514198
9514198