RESUMEN
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.
Asunto(s)
Antipsicóticos/análisis , Benzodiazepinas/análisis , Contaminación de Medicamentos , Antipsicóticos/química , Benzodiazepinas/química , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Excipientes/análisis , Espectroscopía de Resonancia Magnética , Estructura Molecular , Olanzapina , Oxidación-Reducción , Comprimidos , Espectrometría de Masas en Tándem , Tecnología Farmacéutica/métodosRESUMEN
Rabeprazole sodium [1] is a proton pump inhibitor, used as an antiulcerative. During the manufacturing of rabeprazole sodium, we observed an unknown impurity at levels 0.05-0.1% in HPLC analysis along with the known potential impurities. This new unknown impurity was isolated using preparative liquid chromatography. Based on the complete spectral analysis ((1)H NMR, (13)C NMR, DEPT, Mass and IR), this new impurity was designated as 2-[[(3-methyl-4-(methylthio)-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (methylthio impurity of rabeprazole). Impurity isolation, structure elucidation and probable formation mechanism was discussed.