Articolo in rivista, 2020, ENG, 10.1016/j.jpba.2020.113432

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

Aleo, Danilo; Saita, Maria Grazia; Spitaleri, Fabiola; Sanfilippo, Claudia; Patti, Angela

MEDIVIS - Corso Italia, 171 - 95127 Catania, Italy. CNR - Istituto di Chimica Biomolecolare, Via Paolo Gaifami 18, I-95126 Catania, Italy

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.

Journal of pharmaceutical and biomedical analysis (Print) 189

Keywords

Nepafenac, Drug stability, HPLC, alpha-Ketoacid, Benzylic oxidation

CNR authors

Sanfilippo Claudia, Patti Angela

CNR institutes

ICB – Istituto di chimica biomolecolare