Gana Ines, Dugay Annabelle, Henriet Théo, Rietveld Ivo B, Bernard Mélisande, Guechot Christophe, Teulon Jean-Marie, Safta Fathi, Yagoubi Najet, Céolin René, Do Bernard
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.
University of Paris-Descartes, Faculty of Pharmacy, Laboratory of Physical Chemistry, 4 avenue de l'Observatoire, 75006 Paris, France.
J Pharm Biomed Anal. 2014 Aug 5;96:58-67. doi: 10.1016/j.jpba.2014.03.016. Epub 2014 Mar 25.
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.
替诺洛尔是一种具有药理活性的分子，它由酮噻吩、烷基苯甲酸酯和芳基丙醇胺等官能团构成，旨在将利尿剂和β-肾上腺素能受体拮抗剂结合于单个分子中。通过高压液相色谱（HPLC）与具有三重四极杆-线性阱的混合质谱仪联用，已测定了替诺洛尔在多种应激介质中产生的降解产物。采用具有C18-A固定相的Polaris(®)柱和由1%（v/v）三氟乙酸与乙腈混合而成的线性梯度流动相，实现了最佳分离效果。降解产物的结构解析基于MS/MS技术，通过将其碎裂模式与前体数据进行比较来完成。已鉴定出多达七种活性成分的降解产物，这些产物是由水解、氧化、脱水和转酰胺作用产生的，涵盖了具有此类官能团的衍生物一系列可能的降解途径。已对动力学进行了研究，以评估该分子的保质期并确定最重要的降解因素。
