Synthesis and characterization of impurities of an anti-psychotic drug substance, Olanzapine

Abstract

HPLC analysis of olanzapine 1, a known anti-psychotic drug, showed impurity peaks ranging from 0.05 to 0.15 % during process development. These samples were analyzed by LCMS and the peaks were identified at m/z 230, 341, 511, 326, 361 and 329. All six impurities were synthesized individually and characterized based on their spectral data (IR, NMR and Mass). The structure of these impurities were assigned as 2-methyl-4,9-dihydro-3-thia-4,9-diazabenzo[f]azulen- 10-one 4, 1-[4-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulen-10-yl) piperazin-1-yl]ethanone 5, bis-[10-(2-methyl-4H-3-thia-4,9-diazabenzo[f]azulene) ]-1,4-piperazine 6, 2,4-dimethyl-10-(4-methylpiperazin-1-yl)-4H-3-thia-4,9- diazabenzo[f]azulene 7, 10-(4-chloromethyl-4-methylpiperazin-1-ylium)-2-methyl- 4H-3-thia-4,9-diazabenzo[f]azulene chloride 8 and 2-methyl-10-(4-methyl-N- oxopiperazin-1-yl)-4H-3-thia-4,9-diazabenzo[f]azulene 9 respectively. The formation, synthesis and characterisation of the olanzapine impurities are discussed. ©ARKAT USA, Inc.