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

作者：Gana Ines; Dugay Annabelle; Henriet Theo; Rietveld Ivo B; Bernard Melisande; Guechot Christophe; Teulon Jean Marie; Safta Fathi; Yagoubi Najet; Ceolin Rene; Do Bernard^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2014, 96: 58-67.

DOI：10.1016/j.jpba.2014.03.016

• Tienoxolol
• Degradation pathways
• Liquid chromatography-mass spectrometry
• Kinetics
• Active pharmaceutical ingredient

Tienoxolol is a pharmacologically active molecule designed with the functional groups ketothiophene, alkyl benzoate and arylpropanolamine so as to combine a diuretic and a p-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 (R) 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.

• 出版日期2014-8-5