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

Liquid chromatography (LC)-NMR spectroscopy was used to obtain detailed inf ormation regarding the structure of a bulk drug impurity present in glycina mide ribonucleotide transformylase (GART) inhibitor AG2034. The LC-NMR expe riments (1D H-1 and 2D TOCSY) were performed in the stop-flow mode on crude retained impurity-enriched samples of the synthetic precursor to AG2034. C omparative 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 informatio n derived from both LC-NMR and LC-MS data provided insights into purificati on methods, which ultimately led to the full characterization of the impuri ty by high-resolution NMR spectroscopy. Copyright (C) 1999 John Wiley & Son s, Ltd.