title: Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide.
abstract: Galantamine hydrobromide was subjected to different stress conditions (acidic, alkaline, thermal, photolytic and oxidative). Degradation was found to occur under acidic, photolytic and oxidative conditions, while the drug was stable under alkaline and elevated temperature conditions. A stability-indicating reversed-phase liquid chromatographic method was developed for the determination of the drug in the presence of its degradation products. The method was validated for linearity, precision, accuracy, specificity, selectivity and intermediate precision. Additionally, the degradation kinetics of the drug was assessed in relevant cases. The kinetics followed a first order behavior in the case of acidic and photolytic degradation, while a two-phase kinetics behavior was found for the oxidative degradation. The degradation products were characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Dehydration, epimerization and N-oxidation were the main processes observed during the degradation of galantamine. Moreover, if sufficient material could be isolated the inhibitory activity against the target enzyme acetylcholinesterase was also assessed.
authors.affiliation: VU University Amsterdam, Faculty of Sciences, 1081 HV Amsterdam, The Netherlands.
authors.forename: Lygia Azevedo
authors.initials: LA
authors.lastname: Marques
authors.forename: Ismail
authors.initials: I
authors.lastname: Maada
authors.forename: Frans J J
authors.initials: FJ
authors.lastname: de Kanter
authors.forename: Henk
authors.initials: H
authors.lastname: Lingeman
authors.forename: Hubertus
authors.initials: H
authors.lastname: Irth
authors.forename: Wilfried M A
authors.initials: WM
authors.lastname: Niessen
authors.forename: Martin
authors.initials: M
authors.lastname: Giera
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D002800:Cholinesterase Inhibitors / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D002802:Cholinesterases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005702:Galantamine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D006358:Hot Temperature / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light / Q000009:adverse effects; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010782:Photolysis; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical
chemical_list: D002800:Cholinesterase Inhibitors; D005702:Galantamine; D002802:Cholinesterases