Structural characterization of pharmaceutical heparins prepared from different animal tissues

J Pharm Sci. 2013 May;102(5):1447-57. doi: 10.1002/jps.23501. Epub 2013 Mar 21.

Abstract

Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. Three heparins from porcine, ovine, and bovine were characterized through state-of-the-art carbohydrate analysis methods with a view profiling their physicochemical properties. Differences in molecular weight, monosaccharide and disaccharide composition, oligosaccharide sequence, and antithrombin III-binding affinity were observed. These data provide some insight into the variability of heparins obtained from these three species and suggest some analytical approaches that may be useful in confirming the species origin of a heparin active pharmaceutical ingredient.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticoagulants / chemistry*
  • Anticoagulants / pharmacology
  • Antithrombin III / metabolism
  • Carbohydrate Sequence
  • Cattle
  • Heparin / chemistry*
  • Heparin / pharmacology
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Oligosaccharides / analysis*
  • Protein Binding
  • Sheep
  • Species Specificity
  • Spectrometry, Mass, Electrospray Ionization
  • Surface Plasmon Resonance
  • Swine

Substances

  • Anticoagulants
  • Oligosaccharides
  • Antithrombin III
  • Heparin