Sequencing the Oligosaccharide Pool in Dalteparin Sodium with Offline Strong Anion Exchange (SAX)-HPLC and ESI-MS/MS

Wang, Z.
Zhang, T.
Xie, S.
Liu, X.
Li, H.
Linhardt, Robert J.
Chi, L.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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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.
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.
Carbohydrate Polymers, 183, 81-90
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