Evaluation of paclitaxel rearrangement involving opening of the oxetane ring and migration of acetyl and benzoyl groups

The stability of drug is a critical factor in quality control, drug efficacy, safety, storage, and production conditions. The rearrangement of paclitaxel, which involves opening of the oxetane ring and migration of acetyl group occurred on heating a powder of purified paclitaxel. Subsequently, the u...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2007-02, Vol.43 (3), p.1141-1145
Main Authors: Pyo, Sang-Hyun, Cho, Jin-Suk, Choi, Ho-Joon, Han, Byung-Hee
Format: Article
Language:English
Subjects:
Acetyl migration
Analysis
Analytical, structural and metabolic biochemistry
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Benzoyl migration
Biological and medical sciences
Cell Line, Tumor
Chromatography, High Pressure Liquid
Female
Fundamental and applied biological sciences. Psychology
General pharmacology
Humans
Indicators and Reagents
KB Cells
Magnetic Resonance Spectroscopy
Medical sciences
Oxetane ring opening
Paclitaxel
Paclitaxel - analogs & derivatives
Paclitaxel - chemistry
Paclitaxel - pharmacology
Pharmacology. Drug treatments
Rearrangement
Tetrazolium Salts
Thiazoles
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Summary:The stability of drug is a critical factor in quality control, drug efficacy, safety, storage, and production conditions. The rearrangement of paclitaxel, which involves opening of the oxetane ring and migration of acetyl group occurred on heating a powder of purified paclitaxel. Subsequently, the unusual migration of benzoyl groups progressed rapidly in organic solvents. These rearrangement derivatives were isolated carefully. The structures of the intermediate derivative A and the product derivative B were confirmed using 1H NMR, high performance liquid chromatography (HPLC), and mass spectrometry. We proposed the rearrangement pathway here for the first time. Neither derivative exhibited bioactivity in SKOV3 (ovarian cancer) or MDA-MB-435 (breast cancer) cell culture assays.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2006.08.026