Analysis of 2,2'-Azobis (2-amidinopropane) dihydrochloride degradation and hydrolysis in aqueous solutions

Jay Werber, Y. John Wang, Michael Milligan, Xiaohua Li, Junyan A. Ji

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH), a free radical-generating azo compound, is gaining prominence as a model oxidant in small molecule and protein therapeutics, namely for its ability to initiate oxidation reactions via both nucleophilic and free radical mechanisms. To better understand its degradation pathways, AAPH was degraded at 40°C in aqueous solutions over a wide pH range. Samples were analyzed via liquid chromatography-ultraviolet spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The thermal decomposition rate of AAPH to form radical species averaged 2.1 × 10-6 s-1 and did not vary significantly with pH. The hydrolysis rate increased exponentially with pH, showing hydroxide ion dependence. A mechanism for AAPH hydrolysis is proposed. The LC-MS/MS results provided evidence that the alkoxyl radical is a major radical species in solution. The LC-MS/MS results also showed a radical disproportionation reaction and enabled the generation of an overall reaction scheme showing the various side and termination products of AAPH degradation.

Original languageEnglish (US)
Pages (from-to)3307-3315
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • AAPH
  • ABAP
  • Azonitrile
  • Free radicals
  • Liquid chromatographymass spectrometry
  • Oxidation
  • Polysorbate
  • Stability
  • Surfactants

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