title: Identification of the major degradation pathways of ticagrelor.
abstract: 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.
authors.affiliation: Université Paris Sud, UFR de Pharmacie, UA 401 « Matériaux et Santé ». 5, rue Jean Baptiste Clément, 92296 Châtenay-Malabry, France; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Pharmacie 47-83 Boulevard de l'Hôpital, 75013 Paris, France. Electronic address: hassane.sadou-yaye@psl.aphp.fr.
authors.forename: Hassane
authors.initials: H
authors.lastname: Sadou Yayé
authors.affiliation: Université Paris Sud, UFR de Pharmacie, UA 401 « Matériaux et Santé ». 5, rue Jean Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Philippe-Henri
authors.initials: PH
authors.lastname: Secrétan
authors.affiliation: Université Paris Sud, UFR de Pharmacie, UA 401 « Matériaux et Santé ». 5, rue Jean Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Théo
authors.initials: T
authors.lastname: Henriet
authors.affiliation: Université Paris Sud, UFR de Pharmacie, UA 401 « Matériaux et Santé ». 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: Mélisande
authors.initials: M
authors.lastname: Bernard
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: Fatma
authors.initials: F
authors.lastname: Amrani
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: Wiem
authors.initials: W
authors.lastname: Akrout
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Pharmacie 47-83 Boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tilleul
authors.affiliation: Université Paris Sud, UFR de Pharmacie, UA 401 « Matériaux et Santé ». 5, rue Jean Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Najet
authors.initials: N
authors.lastname: Yagoubi
authors.affiliation: Université Paris Sud, UFR de Pharmacie, UA 401 « Matériaux et Santé ». 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: Bernard
authors.initials: B
authors.lastname: Do
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000528:radiation effects; D056148:Chromatography, Reverse-Phase / Q000295:instrumentation / Q000379:methods*; D004340:Drug Contamination; D004355:Drug Stability; D006358:Hot Temperature; D006868:Hydrolysis; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010782:Photolysis; D010975:Platelet Aggregation Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D058921:Purinergic P2Y Receptor Antagonists / Q000032:analysis* / Q000737:chemistry / Q000528:radiation effects; D015203:Reproducibility of Results; D000077486:Ticagrelor
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: Degradation kinetic; Degradation pathways; Electrospray orbitrap mass spectrometry; LC stability-indicating assay method; Ticagrelor