Degradation study of the investigational anticancer drug clanfenur

Clanfenur belongs to a new group of substituted benzoylphenylureas. The drug shows both in vitro and in vivo antitumour activity. To assess its chemical stability, a study was carried out in which the effect of pH, temperature, ionic strength and buffer concentration on the reaction rate constant k...

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Bibliographic Details
Published in:International journal of pharmaceutics 1999-08, Vol.185 (2), p.227-235
Main Authors: Sluiter, C., Kettenes-van den Bosch, J.J., Hop, E., van der Houwen, O.A.G.J., Underberg, W.J.M., Bult, A.
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic agents
Antineoplastic Agents - pharmacokinetics
Biological and medical sciences
Buffers
Chromatography, High Pressure Liquid
Clanfenur
Cytostatic
Degradation products
Diflubenzuron - analogs & derivatives
Diflubenzuron - pharmacokinetics
Drug Stability
General aspects
General pharmacology
Hydrogen-Ion Concentration
Kinetics
LC-ESI-MS
Mass Spectrometry
Medical sciences
Osmolar Concentration
Pharmacology. Drug treatments
Reproducibility of Results
Solutions
Spectrophotometry, Ultraviolet
Stability
Water - chemistry
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Summary:Clanfenur belongs to a new group of substituted benzoylphenylureas. The drug shows both in vitro and in vivo antitumour activity. To assess its chemical stability, a study was carried out in which the effect of pH, temperature, ionic strength and buffer concentration on the reaction rate constant k obs were examined. A stability-indicating reversed-phase high performance liquid chromatography (RP-HPLC) system was used. The pH-log k obs degradation profile, obtained at 70°C, shows that clanfenur has its maximum stability in the pH region 4–5. At pH 7, half-lives were calculated by extrapolation of the Arrhenius plot; at 4°C the half-life was calculated to be 141 years and at 25°C 9.5 years. The activation energy was calculated to be 114 kJ/mol. In acidic, neutral, and alkaline media, the ionic strength has no effect on the degradation. The buffer concentration of citrate, phosphate, borate, and carbonate did not affect the value of k obs. An RP-HPLC chromatogram of degraded clanfenur shows the presence of four degradation products, three of which were identified by LC-ESI-MS as p-chloroaniline, p-chlorophenylurea and 2-fluoro-6-dimethylaminobenzamide.
ISSN:0378-5173
1873-3476
DOI:10.1016/S0378-5173(99)00160-X