Degradation pathways study of the natriuretic and β-adrenoceptor antagonist tienoxolol using liquid chromatography–electrospray ionization multistage mass spectrometry

Abstract Tienoxolol is a pharmacologically active molecule designed with the functional groups ketothiophene, alkyl benzoate and arylpropanolamine so as to combine a diuretic and a β-adrenoreceptor antagonist into a single molecule. Its degradation products generated in several stress media have been determined by high-pressure liquid chromatography (HPLC) coupled to a hybrid mass spectrometer with a triple quadrupole-linear trap. A Polaris ® column with a C18-A stationary phase and a linear gradient mobile phase composed of a mixture of trifluoroacetic acid 1% ( v / v ) and acetonitrile allowed for optimal separation. Structural elucidation of the degradation products has been based on MS / MS techniques, by comparing their fragmentation patterns to the precursor's data. Up to seven degradation products of the active ingredient, resulting from hydrolysis, oxidation, dehydration and transamidation have been identified, covering a range of possible degradation pathways for derivatives with such functional groups. Kinetics have been studied to assess the molecule's shelf life and to identify the most important degradation factor.