Structural elucidation of the tetrasaccharide pool in enoxaparin sodium

Anal Bioanal Chem. 2012 Jul;403(9):2733-44. doi: 10.1007/s00216-012-6045-0. Epub 2012 May 18.

Abstract

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 β-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.

MeSH terms

  • Anticoagulants / chemistry*
  • Carbohydrate Sequence
  • Electrophoresis, Capillary
  • Enoxaparin / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Oligosaccharides / analysis*
  • Oligosaccharides / isolation & purification
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Anticoagulants
  • Enoxaparin
  • Oligosaccharides