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

doi:10.1208/s12249-012-9784-5

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

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	661-673
Number of pages	13
Journal	AAPS PharmSciTech
Volume	13
Issue number	2
DOIs	https://doi.org/10.1208/s12249-012-9784-5
State	Published - Jun 2012

Keywords

CPS49
NSC-726796
NSC-749820
preformulation
stability

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1208/s12249-012-9784-5

Cite this

@article{75450a25fc98484a869691cad0762ea6,

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.",

keywords = "CPS49, NSC-726796, NSC-749820, preformulation, stability",

author = "Duoli Guo and Cain, {James P.} and Sean O'Connell and Gardner, {Erin R.} and Steven Pisle and Figg, {William D.} and Tabibi, {S. Esmail} and Yalkowsky, {Samuel H.}",

note = "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.",

year = "2012",

month = jun,

doi = "10.1208/s12249-012-9784-5",

language = "English (US)",

volume = "13",

pages = "661--673",

journal = "AAPS PharmSciTech",

issn = "1530-9932",

publisher = "American Association of Pharmaceutical Scientists",

number = "2",

}

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

UR - http://www.scopus.com/inward/citedby.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 -

Preformulation study of NSC-726796

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this