MS/MS AND HPLC CHARACTERIZATION OF FORCED DEGRADATION PRODUCTS OF DUTASTERIDE AND TAMSULOSIN HYDROCHLORIDE

A new simple and sensitive reverse phase high performance liquid chromatographic method was developed for simultaneous estimation of Dutasteride and Tamsulosin hydrochloride following forced degradation studies as per ICH guidelines. The degradation products were observed in acid and alkaline hydrolysis for Dutasteride; whereas Tamsulosin hydrochloride showed degradation on exposure to light. All the degradants were separated by preparative thin layer chromatography and subjected to structural elucidation by mass spectrometry using electron spray ionization technique. The base peak of DTS with m/z of 529.1 was formed in positive ESI mode. The daughter ion of DTS was observed at m/z of 461.2. Two degradants with m/z of 546.2 and m/z of 527.5 were formed by acid hydrolysis to give a carboxylic acid derivative and another by dehydrogenation respectively.  Degradation product with m/z of 573.3was di-sodium adduct of DTS and was formed only in alkaline hydrolytic condition. The base peak of photo degradant of TMS with m/z of 409.1 was formed in positive ESI mode showed same m/z value of the base peak of TMS. This indicated that under photolytic degradation only structural modification occurred in TMS molecule. The mechanisms for the formation of degradation products for DTS and TMS are presented in the paper. A linear gradient mode of elution was used for separation of DTS, TMS and their degradants on a Hi Q Sil C18HS column using a UV detector. The developed method was validated and used for the analysis of marketed tablets of DTS and TMS in combination.