title: 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.
authors.affiliation: University of Paris-Descartes, Faculty of Pharmacy, Laboratory of Physical Chemistry, 4 avenue de l'Observatoire, 75006 Paris, France; University of Monastir, Faculty of Pharmacy, Laboratory of Analytical Chemistry, rue Ibn Sian, 5000 Monastir, Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Gana
authors.affiliation: University of Paris-Descartes, Faculty of Pharmacy, Laboratory of Physical Chemistry, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Dugay
authors.affiliation: University of Paris-Sud, Faculty of Pharmacy, Groupe Matériaux et Santé EA 401, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France; Assistance Publique-Hôpitaux de Paris, Agence Générale des Equipements et Produits de Santé, Département de Contrôle Qualité et Développement Analytique, 7 rue du Fer à Moulin, 75005 Paris, France.
authors.forename: Théo
authors.initials: T
authors.lastname: Henriet
authors.affiliation: University of Paris-Descartes, Faculty of Pharmacy, Laboratory of Physical Chemistry, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Ivo B
authors.initials: IB
authors.lastname: Rietveld
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Agence Générale des Equipements et Produits de Santé, Département de Contrôle Qualité et Développement Analytique, 7 rue du Fer à Moulin, 75005 Paris, France.
authors.forename: Mélisande
authors.initials: M
authors.lastname: Bernard
authors.affiliation: Solvay SA, 25 rue de Clichy, 75009 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Guechot
authors.affiliation: 78170 La Celle St Cloud, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Teulon
authors.affiliation: University of Monastir, Faculty of Pharmacy, Laboratory of Analytical Chemistry, rue Ibn Sian, 5000 Monastir, Tunisia.
authors.forename: Fathi
authors.initials: F
authors.lastname: Safta
authors.affiliation: University of Paris-Sud, Faculty of Pharmacy, Groupe Matériaux et Santé EA 401, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Najet
authors.initials: N
authors.lastname: Yagoubi
authors.affiliation: University of Paris-Descartes, Faculty of Pharmacy, Laboratory of Physical Chemistry, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: René
authors.initials: R
authors.lastname: Céolin
authors.affiliation: University of Paris-Sud, Faculty of Pharmacy, Groupe Matériaux et Santé EA 401, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France; Assistance Publique-Hôpitaux de Paris, Agence Générale des Equipements et Produits de Santé, Département de Contrôle Qualité et Développement Analytique, 7 rue du Fer à Moulin, 75005 Paris, France. Electronic address: bernard.do@parisdescartes.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Do
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D011412:Propanolamines / Q000032:analysis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C056983:tienoxolol
keywords: Active pharmaceutical ingredient; Degradation pathways; Kinetics; Liquid chromatography–mass spectrometry; Tienoxolol