Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
2713362
Reference Type
Journal Article
Title
Direct evidence of 2-cyano-2-propoxy radical activity during AIBN-based oxidative stress testing in acetonitrile-water solvent systems
Author(s)
Watkins, MA; Pitzenberger, S; Harmon, PA
Year
2013
Is Peer Reviewed?
Yes
Journal
Journal of Pharmaceutical Sciences
ISSN:
0022-3549
EISSN:
1520-6017
Volume
102
Issue
5
Page Numbers
1554-1568
Language
English
PMID
23494859
DOI
10.1002/jps.23500
Web of Science Id
WOS:000317620200017
URL
http://
://WOS:000317620200017
Exit
Abstract
Oxidative susceptibility testing was performed on a drug substance containing a methoxy-naphthalene moiety. 2,2-azobisisobutyronitrile (AIBN) was employed to initiate peroxy radical oxidation to mimic autoxidation processes. In acetonitrile (ACN)water solvents, three major degradation products are formed. However, addition of small amounts of methanol to the solvent system completely eliminated the observed degradation products. To understand this effect, the structures of the three degradants have been elucidated using nuclear magnetic resonance, liquid chromatographytandem mass spectrometry, and accurate mass Fourier transform ion cyclotron resonance mass spectrometry. One degradant structure definitively proves the degradation resulted from alkoxy radicals (2-cyano-2 propoxy radical) arising from the disproportionation of the tertiary AIBN-derived peroxy radicals, rather than from the intended action of the AIBN peroxy radicals themselves. The reaction occurs over a wide range of AIBN and drug substance concentrations. This protective effect of several percent methanol by volume is rationalized by known methanol H atom donation rates to similar tert-butoxy and cumyloxy radicals (ca. 10 M1 s1) and the high methanol concentration relative to the dilute substrate being investigated. This work confirms recent proposals for addition of at least about 10% methanol to the standard ACNwater AIBN stress testing diluent to insure that only the desired peroxy radical activity is present during the oxidative stress test. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:15541568, 2013
Keywords
analysis; antioxidants; chemical stability; forced conditions; free radicals; oxidation
Tags
IRIS
•
Naphthalene
Previous HERO references
Database Searches
WOS
Combined data set
Data set for title/abstract screening
Excluded - PECO criteria not met (TIAB)
OPPT
•
3-Methoxybutyl acetate
Literature Search
Human Health
WOS (private)
Fate
WOS (private)
Environmental Hazard
WOS (private)
Other
•
Naphthalene (2021 Evidence mapping publication)
Previous HERO references
Database Searches
WOS
Combined data set
Data set for title/abstract screening
Excluded – PECO criteria not met
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity