Sequencing the Oligosaccharide Pool in Dalteparin Sodium with Offline Strong Anion Exchange (SAX)-HPLC and ESI-MS/MS
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Authors
Wang, Z.
Zhang, T.
Xie, S.
Liu, X.
Li, H.
Linhardt, Robert J.
Chi, L.
Issue Date
2018
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Low molecular weight heparins (LMWHs) are widely used anticoagulant drugs. The composition and sequence of LMWH oligosaccharides determine their safety and efficacy. The short oligosaccharide pool in LMWHs undergoes more depolymerization reactions than the longer chains and is the most sensitive indicator of the manufacturing process. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) has been demonstrated as a powerful tool to sequence synthetic heparin oligosaccharide but never been applied to analyze complicated mixture like LMWHs. We established an offline strong anion exchange (SAX)-high performance liquid chromatography (HPLC) and ESI-MS/MS approach to sequence the short oligosaccharides of dalteparin sodium. With the help of in-house developed MS/MS interpretation software, the sequences of 18 representative species ranging from tetrasaccharide to octasaccharide were obtained. Interestingly, we found a novel 2,3-disulfated hexauronic acid structure and reconfirmed it by complementary heparinase digestion and LC-MS/MS analysis. This approach provides straightforward and in-depth insight to the structure of LMWHs and the reaction mechanism of heparin depolymerization.
Description
Carbohydrate Polymers, 183, 81-90
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
Sequencing the Oligosaccharide Pool in Dalteparin Sodium with Offline Strong Anion Exchange (SAX)-HPLC and ESI-MS/MS, Z. Wang, T. Zhang, S. Xie, X. Liu, H. Li, R. J. Linhardt, L. Chi, Carbohydrate Polymers, 183, 81-90, 2018.