1017241-36-9Relevant articles and documents
Isolation, identification, and synthesis of two oxidative degradation products of olanzapine (LY170053) in solid oral formulations
Baertschi, Steven W.,Brunner, Heiko,Bunnell, Charles A.,Cooke, Gary G.,Diseroad, Benjamin,Dorman, Douglas E.,Jansen, Patrick J.,Kemp, Craig A. J.,Maple, Steven R.,McCune, Karen A.,Speakman, Jeffrey L.
, p. 883 - 892 (2008)
Two impurities found in both stressed and aged solid-state formulations of olanzapine have been identified as (Z)-1,3-dihydro-4-(4-methyl-1-piperazinyl)-2- (2-oxopropylidene)-2H-1,5-benzodiazepin-2-one (1) and (Z)-1-[1,2-dihydro-4-(4- methyl-1-piperazinyl)-2-thioxo-3H-1,5-benzodiazepin-3-ylidene]propan-2-one (2). The structures indicate that the two impurities are degradation products resulting from oxidation of the thiophene ring of olanzapine. The impurities were isolated by preparative HPLC from a thermally stressed formulation, and characterized by UV, IR, MS, and NMR. A synthetic preparation of compounds 1 and 2 by reaction of olanzapine with the singlet oxygen mimic 4-phenyl-1,2,4- triazoline-3,5-dione (PTAD) is presented. The structure of 2 was also determined by single-crystal X-ray diffraction analysis. A degradation pathway for the formation of 1 and 2 is proposed.