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Application of LC–NMR to the identification of bulk drug impurities in GART inhibitor AG2034

✍ Scribed by Barbara C. M. Potts; Kim F. Albizati; Mark O’Neil Johnson; Joyce Prosser James


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
120 KB
Volume
37
Category
Article
ISSN
0749-1581

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✦ Synopsis


Liquid chromatography (LC)-NMR spectroscopy was used to obtain detailed information regarding the structure of a bulk drug impurity present in glycinamide ribonucleotide transformylase (GART) inhibitor AG2034. The LC-NMR experiments (1D 1 H and 2D TOCSY) were performed in the stop-flow mode on crude retained impurityenriched samples of the synthetic precursor to AG2034. Comparative analysis of the data for the parent compound with those for the impurity indicated that the impurity was nearly a dimer of the parent, and allowed all major substructures to be delineated. The structural information derived from both LC-NMR and LC-MS data provided insights into purification methods, which ultimately led to the full characterization of the impurity by high-resolution NMR spectroscopy.