title: A new derivative detected in accelerated ageing of artesunate-amodiaquine fixed dose combination tablets.
abstract: An unknown impurity detected in small amounts during the heat treatment of artesunate-amodiaquine bilayer tablets was purified by semipreparative HPLC and identified by MS and NMR as the tetrahydrofuranyl acetate-rearranged derivative of anhydrodihydroartemisinin. When anhydrodihydroartemisinin was treated with a Fe(II) salt in acetonitrile-water solution, the same product was generated, together with an isomeric 2-deoxy-4α-hydroxy-anhydrodihydroartemisinin derivative, as expected from the usual homolytic radical opening of the endoperoxide bond previously described for other artemisinin derivatives.
authors.affiliation: Molecular Biodiversity Department, Bertin Pharma, Parc d'activités du Pas du Lac, 78180 Montigny-le-Bretonneux, France. cedric.charrier@bertinpharma.fr
authors.forename: Cedric
authors.initials: C
authors.lastname: Charrier
authors.forename: Gildas
authors.initials: G
authors.lastname: Bertho
authors.forename: Olivier
authors.initials: O
authors.lastname: Petigny
authors.forename: Philippe
authors.initials: P
authors.lastname: Moneton
authors.forename: Robert
authors.initials: R
authors.lastname: Azerad
mesh_terms: D000655:Amodiaquine / Q000032:analysis / Q000737:chemistry*; D000962:Antimalarials / Q000032:analysis / Q000737:chemistry*; D037621:Artemisinins / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004338:Drug Combinations; D004340:Drug Contamination; D004355:Drug Stability; D004356:Drug Storage; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D013607:Tablets
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D013607:Tablets; C515299:amodiaquine, artesunate drug combination; C089918:anhydrodihydroartemisinin; D000655:Amodiaquine