Liquid chromatography electrospray ionization tandem mass spectrometry study of nilutamide and its stress degradation products: in silico toxicity prediction of degradation products.
Biomed Chromatogr
; 28(6): 788-93, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24861745
ABSTRACT
Nilutamide, a nonsteroidal anti-androgen drug, widely used in the treatment of prostate cancer, was subjected to hydrolytic, photolytic, thermal and oxidative stress conditions as per International Conference on Harmonization guidelines Q1A (R2). Nilutamide showed significant degradation under basic hydrolysis and photolytic stress conditions, while it was stable to neutral, acidic and thermal stress conditions. Five degradation products were formed and the chromatographic separation of nilutamide and its degradation products was achieved on a Waters C18 column (4.6 × 250 mm, 5 µm) using a mobile phase consisting of acetonitrile and 0.1% of formic acid in an isocratic elution method. All these degradation products were characterized by LC/MS/MS in negative ion mode, combined with accurate mass measurements. To assign likely structures for the observed degradation products, the fragmentation patterns of the deprotonated drug and its degradation products were compared. The in silico toxicity of the drug and its degradation products was also assessed using TOPKAT software. The carcinogenicity probability of the degradation products, DP-I-IV, was greater than that of nilutamide.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imidazolidinas
/
Antagonistas de Androgênios
Tipo de estudo:
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Biomed Chromatogr
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Índia