AAPS PharmSciTech 2012-06-01

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

Index: AAPS PharmSciTech 13(2) , 661-73, (2012)

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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.


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