title: Preformulation study of NSC-726796.
abstract: A stability-indicating high-performance liquid chromatography method to quantify 2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoroisoindoline-1,3-dione (NSC-726796) and its three main degradation products was developed. This method was used to investigate its degradation kinetics and mechanism. The reaction follows first-order kinetics and appears to be base catalyzed with the maximum stability at pH 1. The products were identified as 2-(2,4-difluorophenylcarbamoyl)-3,4,5,6-tetrafluorobenzoic acid (NSC-749820), 2,4-difluoroaniline, and tetrafluorophthalic acid. The parent drug, NSC-726796, was also found to react with methanol and ethanol. NSC-726796 demonstrates antiangiogenic activity, however, when its degradant NSC749820 does not show antiangiogenic activity.
authors.affiliation: College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA. duoliguo@gmail.com
authors.forename: Duoli
authors.initials: D
authors.lastname: Guo
authors.forename: James P
authors.initials: JP
authors.lastname: Cain
authors.forename: Sean
authors.initials: S
authors.lastname: O'Connell
authors.forename: Erin R
authors.initials: ER
authors.lastname: Gardner
authors.forename: Steven
authors.initials: S
authors.lastname: Pisle
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: S Esmail
authors.initials: SE
authors.lastname: Tabibi
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Yalkowsky
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D000432:Methanol / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010795:Phthalic Acids / Q000737:chemistry; D010797:Phthalimides / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D046509:Tissue Culture Techniques
chemical_list: C575354:2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoroisoindoline-1,3-dione; D020533:Angiogenesis Inhibitors; D000814:Aniline Compounds; D010795:Phthalic Acids; D010797:Phthalimides; D012997:Solvents; D000431:Ethanol; C043454:2,4-difluoroaniline; D000432:Methanol