Journal
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
Volume 403, Issue 9, Pages 2733-2744Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-012-6045-0
Keywords
Low-molecular-weight heparin; Enoxaparin sodium; Tetrasaccharide; Heparinases; Nuclear magnetic resonance; Mass spectrometry
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Low-molecular-weight heparins (LMWHs) are produced from heparin by various depolymerization strategies, which result in a reduction of the average molecular weight of the polysaccharide chains, a reduction of the anti-factor IIa activity (and a concomitant increase in the anti-factor Xa/anti-factor IIa ratio), and introduction of process-related structural signatures. Numerous techniques have been developed to characterize LMWHs and to measure the type and extent of structural modifications that are introduced as a function of the depolymerization process. We present here an analysis of the tetrasaccharide pool of enoxaparin sodium, a LMWH produced by chemical beta-elimination of heparin benzyl ester. We identify the predominant sequences present within the tetrasaccharide pool and demonstrate that this pool provides a sensitive, specific readout of the physicochemical process conditions used to generate enoxaparin sodium.
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