Identification and characterization of stress degradation products of dronedarone hydrochloride employing LC-UV/PDA, LC-MS/TOF and MS(n) studies

Dronedarone HCl was subjected to forced decomposition conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH guideline Q1A(R2). The drug showed significant degradation under alkaline hydrolytic and alkaline photolytic conditions whi...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2016-01, Vol.118, p.139-148
Main Authors: Chadha, Renu, Bali, Alka, Bansal, Gulshan
Format: Article
Language:English
Subjects:
Amiodarone - analogs & derivatives
Amiodarone - analysis
Amiodarone - metabolism
Chromatography, Liquid - methods
Spectrophotometry, Ultraviolet - methods
Tandem Mass Spectrometry - methods
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dronedarone HCl was subjected to forced decomposition conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH guideline Q1A(R2). The drug showed significant degradation under alkaline hydrolytic and alkaline photolytic conditions while it remained stable in neutral, acidic, thermal and oxidative conditions. In total, six degradation products (I-VI) were formed, which could be separated by chromatography on C18 (250 mm × 4.6 mm; 5 μ, Xterra) column using isocratic elution method. Detection wavelength was selected as 288 nm. Multi-stage (MS(n)) and MS/TOF accurate mass studies were carried out to establish the complete fragmentation pathway of the drug which in turn was utilized in characterization of the products. The degradation pathway of the drug leading to generation of products I-VI was postulated and this has not been reported so far.
ISSN:1873-264X
DOI:10.1016/j.jpba.2015.10.028