Identification of impurities in acarbose by using an integrated liquid chromatography-nuclear magnetic resonance and liquid chromatography-mass spectrometry approach

J Sep Sci. 2005 Aug;28(13):1442-7. doi: 10.1002/jssc.200400057.

Abstract

The usefulness of applying an integrated LC-NMR and LC-MS approach to acarbose bulk drug impurity profiling is demonstrated. LC-MS and LC-NMR methodologies were employed for the online separation and structural elucidation of a final drug product. Combining data provided by the stop-flow LC-NMR and LC-MS experiments made it possible to identify the main components present in the acarbose sample. Spectral analysis revealed that A and B were known impurities while C was an unknown compound. LC-MS and LC-NMR analyses revealed that C was a pentasaccharide differing from the acarbose in number and nature of sugar subunits in the molecule. It was subsequently isolated and its structure was confirmed by the offline 1- and 2-D NMR experiments, and atom assignment was made.

MeSH terms

  • Acarbose / chemistry*
  • Carbohydrate Sequence
  • Chromatography, Liquid / methods
  • Gas Chromatography-Mass Spectrometry / methods
  • Hypoglycemic Agents / chemistry
  • Magnetic Resonance Spectroscopy / methods
  • Mass Spectrometry / methods
  • Models, Molecular
  • Molecular Sequence Data

Substances

  • Hypoglycemic Agents
  • Acarbose