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Application of LC–NMR to the identification of bulk drug impurities in GART inhibitor AG2034
Author(s) -
Potts Barbara C. M.,
Albizati Kim F.,
Johnson Mark O’Neil,
James Joyce Prosser
Publication year - 1999
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/(sici)1097-458x(199906)37:6<393::aid-mrc468>3.0.co;2-q
Subject(s) - chemistry , impurity , nuclear magnetic resonance spectroscopy , spectroscopy , chromatography , proton nmr , analytical chemistry (journal) , stereochemistry , organic chemistry , physics , quantum mechanics
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 impurity‐enriched 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. Copyright © 1999 John Wiley & Sons, Ltd.