Degradation profile of nepafenac in aqueous solution and structural characterization of a novel degradation product

The stability of the anti-inflammatory drug nepafenac was investigated in aqueous solutions containing hydroxypropyl-beta-cyclodextrin at three different values of pH and degradation products were identified. (2-Amino-3-benzoyl)-oxoacetic acid, previously not reported as nepafenac-related impurity, was isolated and structurally characterized by NMR and ESI-MS analyses. It was also shown that the formation of this a-ketoacid from nepafenac in alkaline water/organic cosolvent solution occurs through an aerobic oxidation of the key intermediate 7-benzoyl-1,3-dihydro-indol-2-one, which in some extent is protected from oxidation in the presence of the cyclodextrin additive. (C) 2020 Elsevier B.V. All rights reserved.