LC and LC–MS study for simultaneous determination of tramadol hydrochloride and ketorolac tromethamine in bulk and formulation with their major degradation products

Abstract

The present work was aimed to separate, identify and characterize the major degradation products of tramadol hydrochloride and ketorolac tromethamine. A rapid, specific and accurate stability indicating reversed phase liquid chromatographic method has been developed for simultaneous determination of tramadol hydrochloride and ketorolac tromethamine in bulk and formulation. The drugs were subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolytic and thermal stress, as per ICH guidelines. The separation, identification and characterization of major stressed degradation products were performed using high performance liquid chromatography combined with quadrupole electrospray ionization mass spectroscopy (LC/ESI-MS) on a C-18 column. Tramadol hydrochloride was found to degrade in acidic and oxidative conditions while ketorolac tromethamine undergoes extensive degradation under oxidative, UV and acid hydrolysis stress.From the mass spectral data, probable structures were assigned to the degradation products. The identified major degradation product for tramadol under acid stress may be 1-(3′-methoxy-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)-N,N-dimethylmethanamine. Ketorolac tromethamine was also found to convert in to numerous degradation products under oxidative stress.