title: Synthesis and characterization of new related substances of the antiarrhythmic drug dronedarone hydrochloride.
abstract: Two new potential impurities of antiarrhythmic drug substance Dronedarone Hydrochloride together with debutyldronedarone were detected by LC-MS analysis during process development. A successful synthetic strategy for the synthesis of these potential impurities was developed facilitating the access to new impurity reference standards. Their synthesis and characterization are discussed in detail. The availability of these impurity standards allowed cost reduction through the increase of process control.
authors.affiliation: Laboratory of Analytical Research and Process Control, Center of Research and Development in Chemistry, National Institute of Industrial Technology, Buenos Aires, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Santos
authors.affiliation: Laboratory of Organic Synthesis, Center of Research and Development in Chemistry, National Institute of Industrial Technology, Buenos Aires, Argentina.
authors.forename: Lia C
authors.initials: LC
authors.lastname: García
authors.affiliation: Laboratory of Analytical Research and Process Control, Center of Research and Development in Chemistry, National Institute of Industrial Technology, Buenos Aires, Argentina.
authors.forename: Cintia
authors.initials: C
authors.lastname: Checura
authors.affiliation: Laboratory of Organic Synthesis, Center of Research and Development in Chemistry, National Institute of Industrial Technology, Buenos Aires, Argentina.
authors.forename: Lucía Gandolfi
authors.initials: LG
authors.lastname: Donadío
authors.affiliation: MAPRIMED S.A., Av Directorio 6155, C1440ATA-CABA, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: MAPRIMED S.A., Av Directorio 6155, C1440ATA-CABA, Argentina.
authors.forename: Hernán
authors.initials: H
authors.lastname: Orgueira
authors.affiliation: Laboratory of Organic Synthesis, Center of Research and Development in Chemistry, National Institute of Industrial Technology, Buenos Aires, Argentina. Electronic address: jcomin@inti.gob.ar.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Comin
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis; D000889:Anti-Arrhythmia Agents / Q000032:analysis* / Q000138:chemical synthesis*; D002623:Chemistry Techniques, Analytical / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D002855:Chromatography, Thin Layer; D000077764:Dronedarone; D004340:Drug Contamination; D015195:Drug Design; D006859:Hydrogen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000889:Anti-Arrhythmia Agents; D006859:Hydrogen; D000077764:Dronedarone; D000638:Amiodarone
keywords: Antiarrhythmic drug; Dronedarone hydrochloride; Impurity profile; LC–MS; Related substances; Synthesis