title: Identification and characterization of stress degradation products of dronedarone hydrochloride employing LC-UV/PDA, LC-MS/TOF and MS(n) studies.
abstract: 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.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Punjab University, Chandigarh 160014, India. Electronic address: renukchadha@rediffmail.com.
authors.forename: Renu
authors.initials: R
authors.lastname: Chadha
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Punjab University, Chandigarh 160014, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Bali
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
authors.forename: Gulshan
authors.initials: G
authors.lastname: Bansal
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D000077764:Dronedarone; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000077764:Dronedarone; D000638:Amiodarone
keywords: Chromatographic; Dronedarone; LC–MS; Stability indicating; Stress degradation; Validation