Identification of the major degradation pathways of ticagrelor
| Autor: | Wiem Akrout, Théo Henriet, Mélisande Bernard, Fatma Amrani, Bernard Do, Najet Yagoubi, P. Tilleul, Philippe-Henri Secrétan, Hassane Sadou Yayé |
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| Rok vydání: | 2015 |
| Předmět: |
Ticagrelor
Adenosine Hot Temperature Clinical Biochemistry Kinetics Pharmaceutical Science Mass spectrometry Mass Spectrometry Analytical Chemistry chemistry.chemical_compound Drug Stability Limit of Detection Impurity Drug Discovery Molecule Ammonium Acetonitrile Spectroscopy Chromatography Reverse-Phase Photolysis Chromatography Molecular Structure Hydrolysis Reproducibility of Results chemistry Forced degradation Purinergic P2Y Receptor Antagonists Degradation (geology) Drug Contamination Oxidation-Reduction Platelet Aggregation Inhibitors |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 105:74-83 |
| ISSN: | 0731-7085 |
| Popis: | Ticagrelor is a direct-acting and reversible P2Y12-adenosine diphosphate (ADP) receptor blocker used as antiplatelet drug. Forced degradation under various stress conditions was carried out. The degradation products have been detected and identified by high-pressure liquid chromatography multistage mass spectrometry (LC-MS(n)) along with high-resolution mass spectrometry. C18 XTerra MS column combined with a linear gradient mobile phase composed of a mixture of 10 mM acetate ammonium/acetonitrile was shown suitable for drug and impurity determinations and validated as a stability indicating method. Structural elucidation of the degradation products relied on MS(n) studies and accurate mass measurements giving access to elemental compositions. Up to nine degradation products resulting from oxidation/auto-oxidation, S-dealkylation and N-dealkylation have been identified, covering a range of possible degradation pathways for derivatives with such functional groups. Kinetics was also studied in order to assess the molecule's shelf-life and to identify the most important degradation factors. |
| Databáze: | OpenAIRE |
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