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 (250mm×4.6mm; 5μ, Nulceodur) column using isocratic elution method. Detection wavelength was selected as 290nm. 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.