Preformulation study of NSC-726796

Duoli Guo*, James P. Cain, Sean O'Connell, Erin R. Gardner, Steven Pisle, William D. Figg, S. Esmail Tabibi, Samuel H. Yalkowsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Pages (from-to)661-673
Number of pages13
JournalAAPS PharmSciTech
Issue number2
StatePublished - Jun 2012
Externally publishedYes


  • CPS49
  • NSC-726796
  • NSC-749820
  • preformulation
  • stability


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