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

•The active substance tienoxolol contains ketothiophene, benzoate and arylpropanolamine groups.•Degradation kinetics were assessed by LC/ESI-MSn.•The structure of degradations products was elucidated by MSn studies.•Hydrolysis, oxidation, dehydration and transamidation have been identified.

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.

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