Degradation study of the investigational anticancer drug clanfenur

Citation
C. Sluiter et al., Degradation study of the investigational anticancer drug clanfenur, INT J PHARM, 185(2), 1999, pp. 227-235
Citations number
13
Categorie Soggetti
Pharmacology & Toxicology
Journal title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN journal
03785173 → ACNP
Volume
185
Issue
2
Year of publication
1999
Pages
227 - 235
Database
ISI
SICI code
0378-5173(19990820)185:2<227:DSOTIA>2.0.ZU;2-G
Abstract
Clanfenur belongs to a new group of substituted benzoylphenylureas. The dru g shows both in vitro and in vivo antitumour activity. To assess its chemic al stability, a study was carried out in which the effect of pH, temperatur e, 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) degradat ion profile, obtained at 70 degrees C, shows that clanfenur has its maximum stability in the pH region 4-5. At pH 7, half-lives were calculated by ext rapolation of the Arrhenius plot; at 4 degrees C the half-life was calculat ed to be 141 years and at 25 degrees C 9.5 years. The activation energy was calculated to be 114 kJ/mol. In acidic, neutral, and alkaline media, the i onic strength has no effect on the degradation. The buffer concentration of citrate, phosphate, berate, and carbonate did not affect the value of k(ob s). An RP-HPLC chromatogram of degraded clanfenur shows the presence of fou r degradation products, three of which were identified by LC-ESI-MS as p-ch loroaniline, p-chlorophenylurea and 2-fluoro-6-dimethylaminobenzamide. (C) 1999 Elsevier Science B.V. All rights reserved.