Identification of forced degradation products of tamsulosin using liquid chromatography/electrospray ionization tandem mass spectrometry

Abstract

A rapid and gradient high-performance liquid chromatography combined with quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC/Q-TOF–ESI-MS/MS) method has been developed for the identification and structural characterization of stressed degradation products of tamsulosin. Tamsulosin, a selective α1-adrenoceptor antagonist, was subjected to forced degradation studies under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions as per ICH guidelines Q1A (R2). The drug degraded significantly under hydrolytic (base and neutral), thermal, oxidative and photolytic conditions, while it was stable to acid hydrolytic stress conditions. A total of twelve degradation products were formed and the chromatographic separation of the drug and its degradation products were achieved on a GRACE C-18 column (250mm×4.6mm, 5μm). All the degradants have been identified and characterized by LC/ESI-MS/MS and accurate mass measurements. To elucidate the structures of degradation products, fragmentation of the [M+H]+ ions of tamsulosin and its degradation products was studied by using LC–MS/MS experiments combined with accurate mass measurements. The product ions of all the protonated degradation products were compared with the product ions of protonated tamsulosin to assign most probable structures for the observed degradation products.