title: Identification of oxidative degradation impurities of olanzapine drug substance as well as drug product.
abstract: Impurities found in stressed and stability studies of olanzapine (polymorphic form-I) [1-7] in both drug substance and drug product are described. These impurities are identified as 4-(4-methyl-1-piperazinyl)-3-hydroxymethylidene-1H-benzo[b][1,4]diazepine-2(3H)-thione (hydroxymethylidene thione) and (Z)-4-(4-methyl-1-piperazinyl)-3-acetoxymethylidene-1H-benzo[b][1,4]diazapine-2(3H)-thione (acetoxymethylidene thione). An oxidative degradation pathway of olanzapine, for the formation of these impurities, has been proposed.
authors.affiliation: Department of Chemical Research, Aurobindo Pharma Ltd Research Centre, 313, Bachupally, Quthubullapur Mandal, Hyderabad 500090, India.
authors.forename: P Sreenivasa
authors.initials: PS
authors.lastname: Rao
authors.forename: Uttam Kumar
authors.initials: UK
authors.lastname: Ray
authors.forename: S G
authors.initials: SG
authors.lastname: Hiriyanna
authors.forename: Sumathi V
authors.initials: SV
authors.lastname: Rao
authors.forename: Hemant Kumar
authors.initials: HK
authors.lastname: Sharma
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Handa
authors.forename: K
authors.initials: K
authors.lastname: Mukkanti
mesh_terms: D014150:Antipsychotic Agents / Q000032:analysis* / Q000737:chemistry; D001569:Benzodiazepines / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D004355:Drug Stability; D005079:Excipients / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D000077152:Olanzapine; D010084:Oxidation-Reduction; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D014150:Antipsychotic Agents; D005079:Excipients; D013607:Tablets; D001569:Benzodiazepines; D000077152:Olanzapine