TY - JOUR
T1 - Preformulation study of NSC-726796
AU - Guo, Duoli
AU - Cain, James P.
AU - O'Connell, Sean
AU - Gardner, Erin R.
AU - Pisle, Steven
AU - Figg, William D.
AU - Tabibi, S. Esmail
AU - Yalkowsky, Samuel H.
N1 - Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts N01-CM-27142 and HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - CPS49
KW - NSC-726796
KW - NSC-749820
KW - preformulation
KW - stability
UR - http://www.scopus.com/inward/record.url?scp=84862882265&partnerID=8YFLogxK
U2 - 10.1208/s12249-012-9784-5
DO - 10.1208/s12249-012-9784-5
M3 - Article
C2 - 22552929
AN - SCOPUS:84862882265
SN - 1530-9932
VL - 13
SP - 661
EP - 673
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
IS - 2
ER -