title: Characterization of stress degradation products of duloxetine hydrochloride employing LC-UV/PDA and LC-MS/TOF studies.
abstract: Duloxetine HCl was subjected to forced degradation under 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 acidic, alkaline and aqueous hydrolytic as well as photolytic conditions. The drug remained stable under thermal and oxidative stress conditions. In total, seventeen degradation products (I-XVII) were formed under varied conditions, which could be separated by chromatography of respective degraded solutions on C18 (250 mm×4.6 mm; 5 μ, Nulceodur) column using isocratic elution method. Detection wavelength was selected as 290 nm. MS/TOF accurate mass studies were carried out to establish the complete fragmentation pathway of the drug and degradation products, which, in turn, was utilized in characterization of the products. The degradation pathway of the drug leading to generation of fifteen products I-X, XII-XIII, XV-XVII was postulated and this has not been reported so far.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab 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, Panjab 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, 147002 Punjab, India.
authors.forename: Gulshan
authors.initials: G
authors.lastname: Bansal
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D000068736:Duloxetine Hydrochloride / Q000737:chemistry*; D006868:Hydrolysis; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010782:Photolysis; D012996:Solutions / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions; D000068736:Duloxetine Hydrochloride
keywords: Chromatographic; Duloxetine; Hydrolytic; LC–MS; Stability indicating; Stress degradation