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.