LC–ESI–MS/MS study of carvedilol and its stress degradation products

Abstract

An isocratic liquid chromatography–electrospray ionization-mass spectrometry (LC–ESI–MS) method has been developed for the separation and identification of stress degradation products (DPs) of carvedilol (CAR), a non-selective β-blocker with vasodilatory properties. CAR was subjected to hydrolytic (acidic, alkaline and neutral), oxidative, photolytic and thermal stress conditions as per ICH guidelines Q1A (R2). The drug degraded under acidic, basic and photolytic stress conditions while it was stable under neutral, thermal and oxidative stress conditions. A total of five DPs were formed which were all well resolved from the parent drug as well as from each other on an Agilent XDB C-18 column (4.6 × 150 mm, 5 μm) using a mobile phase comprising of 20 mM ammonium acetate (pH adjusted to 6) (solvent A) and acetonitrile (solvent B) in an isocratic elution method. The structures of the degradation products were elucidated by using LC–ESI–MS/MS combined with accurate mass measurements.