Identification of impurities in acarbose by using an integrated liquid chromatography-nuclear magnetic resonance and liquid chromatography-mass spectrometry approach.
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.
Novak
Predrag
P
PLIVA Research Institute, Prilaz baruna Filipovica 29, Zagreb, Croatia. predrag.novak@pliva.hr
Cindrić
Mario
M
Tepes
Predrag
P
Dragojević
Snjezana
S
Ilijas
Marina
M
Mihaljević
Kreso
K
D020909:Acarbose / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002853:Chromatography, Liquid / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007004:Hypoglycemic Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data
D007004:Hypoglycemic Agents; D020909:Acarbose