A comprehensive study of apixaban's degradation pathways under stress conditions using liquid chromatography coupled to multistage mass spectrometry - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue RSC Advances Année : 2015

A comprehensive study of apixaban's degradation pathways under stress conditions using liquid chromatography coupled to multistage mass spectrometry

Résumé

© The Royal Society of Chemistry 2015.Apixaban is a novel anticoagulant drug acting as a direct, selective and reversible inhibitor of the coagulation factor Xa. Forced degradation under stress conditions were carried out in order to establish its stability profile. The drug was shown to be stable under photolytic, thermolytic and oxidative conditions, while under hydrolytic conditions, up to seven degradation products were generated for about 15% of drug degradation. The degradation products have been detected by linear gradient reversed phase high-performance liquid chromatography coupled with a photo diode array and with electrospray ionization tandem mass spectrometry. A combination of multistage mass spectrometry and high-resolution mass spectrometry (HR-MS) allowed the structural elucidation. The product ions of the degradation products were compared to those of the apixaban protonated ion so as to assign the most structures possible. This required a study in depth of the drug's fragmentation pattern, which has not been reported so far. In view of the products formed, it appears that hydrolysis of the oxopiperidine moiety of apixaban occurred in acidic medium, whereas that of the tetrahydro-oxo-pyridine moiety would further happen under alkaline conditions. Asides from characterization, the LC method was shown to indicate stability and validated as per the criteria described by the ICH guidelines.
Fichier principal
Vignette du fichier
DOC.pdf (1.6 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03514797 , version 1 (06-01-2022)

Identifiants

Citer

Philippe Henri Secrétan, Hassane Sadou-Yayé, Caroline Aymes-Chodur, Mélisande Bernard, Audrey Solgadi, et al.. A comprehensive study of apixaban's degradation pathways under stress conditions using liquid chromatography coupled to multistage mass spectrometry. RSC Advances, 2015, ⟨10.1039/c5ra00171d⟩. ⟨hal-03514797⟩
62 Consultations
309 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More