Isolation, identification, and synthesis of two oxidative degradation products of olanzapine (LY170053) in solid oral formulations
| Autor: | Speakman Jeffrey Lynn, Gary G. Cooke, Steven R. Maple, Diseroad Benjamin Alan, Heiko Brunner, Charles Arthur Bunnell, Steven W. Baertschi, Patrick J. Jansen, Craig A. J. Kemp, Karen A. McCune, Douglas E. Dorman |
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| Rok vydání: | 2007 |
| Předmět: |
Chromatography
Magnetic Resonance Spectroscopy Singlet oxygen medicine.drug_class Chemistry Pharmaceutical Pharmaceutical Science Atypical antipsychotic Administration Oral Nuclear magnetic resonance spectroscopy High-performance liquid chromatography chemistry.chemical_compound Benzodiazepines chemistry X-Ray Diffraction Impurity Olanzapine X-ray crystallography medicine Thiophene Degradation (geology) Drug Contamination Oxidation-Reduction Chromatography High Pressure Liquid Nuclear chemistry |
| Zdroj: | Journal of pharmaceutical sciences. 97(2) |
| ISSN: | 0022-3549 |
| Popis: | 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. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:883–892, 2008 |
| Databáze: | OpenAIRE |
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