Synthesis of 13C215N2-labeled anti-inflammatory and cytoprotective tricyclic bis(cyanoenone) ([13C215N2]-TBE-31) as an internal standard for quantification by stable isotope dilution LC-MS method

Suqing Zheng, Jeffrey T J Huang, Elena V. Knatko, Sheila Sharp, Maureen Higgins, Iwao Ojima, Albena T. Dinkova-Kostova, Tadashi Honda

Research output: Contribution to journalArticlepeer-review

Abstract

Tricyclic bis(cyanoenone), TBE-31, one of the most potent activators of the Keap1/Nrf2/antioxidant response element pathway, has been developed as a new anti-inflammatory and cytoprotective agent. 13C215N2-labeled TBE-31 ([13C215N2]-TBE-31), which has two 13C and two 15N atoms in two cyano groups, was designed to develop a method for quantification of cell, tissue, and plasma levels of TBE-31 that involves chromatography/mass spectrometry coupledwith the use of a stable isotope-labeled internal standard. [13C215N2]-TBE-31 was successfully synthesized in four steps from a previously reported intermediate, which is prepared in 11 steps from cyclohexanone, by introduction of two 13C atoms with ethyl [13C]formate and two 15N atoms with hydroxyl[15N] amine. The stable isotope dilution liquid chromatography-mass spectrometrymethod for quantification of TBE-31 was successfully developed using [13C215N2]-TBE-31 to compensate for any variables encountered during sample processing and analysis.

Original languageEnglish (US)
Pages (from-to)606-610
Number of pages5
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume57
Issue number10
DOIs
StatePublished - Sep 5 2014

Keywords

  • Anti-inflammatory
  • Carbon-13
  • Cytoprotective
  • Isotopically labeled synthesis
  • Keap1/Nrf2/ARE activator
  • Nitrogen-15
  • Stable isotope dilution LC-MS method

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Drug Discovery
  • Radiology Nuclear Medicine and imaging
  • Biochemistry
  • Medicine(all)

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