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

Benzylic oxidation Drug stability HPLC Nepafenac α-Ketoacid

Journal

Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336

Informations de publication

Date de publication:
10 Sep 2020
Historique:
received: 06 04 2020
revised: 09 06 2020
accepted: 13 06 2020
pubmed: 28 6 2020
medline: 22 6 2021
entrez: 28 6 2020
Statut: ppublish

Résumé

The stability of the anti-inflammatory drug nepafenac was investigated in aqueous solutions containing hydroxypropyl-β-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 α-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.

Identifiants

pubmed: 32592943
pii: S0731-7085(20)31318-2
doi: 10.1016/j.jpba.2020.113432
pii:
doi:

Substances chimiques

Benzeneacetamides 0
Phenylacetates 0
Water 059QF0KO0R
nepafenac 0J9L7J6V8C

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113432

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Danilo Aleo (D)

MEDIVIS - Corso Italia, 171 - 95127 Catania, Italy.

Maria Grazia Saita (MG)

MEDIVIS - Corso Italia, 171 - 95127 Catania, Italy.

Fabiola Spitaleri (F)

MEDIVIS - Corso Italia, 171 - 95127 Catania, Italy.

Claudia Sanfilippo (C)

CNR - Istituto di Chimica Biomolecolare, Via Paolo Gaifami 18, I-95126 Catania, Italy.

Angela Patti (A)

CNR - Istituto di Chimica Biomolecolare, Via Paolo Gaifami 18, I-95126 Catania, Italy. Electronic address: angela.patti@cnr.it.

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Classifications MeSH