A simple and convenient synthesis of labeled 9-hydroxy[¹³C₆]phenanthrene as internal standard for mass spectrometry quantification of a key phenanthrene metabolite in human urines

Abstract

A simple and convenient synthesis of 9-hydroxy[¹³C₆]phenanthrene has been developed from one-ring labeled [¹³C₆]phenanthrene in three steps, involving a copper-ethyl acetate catalyzed “Ullmann-type” reaction. The mild conditions of this nucleophilic aromatic substitution are particularly advantageous in the case of expensive labeled material. Stable-labeled 9-hydroxy[¹³C₆]phenanthrene has proven to be an ideal [M + 6]isotopomer for use as an internal standard for quantification of OH-polycyclic aromatic hydrocarbons by gas chromatography with tandem mass spectrometry (GC-MS/MS) in human urines.

Graphical Abstract

Keywords:

• Polycyclic aromatic hydrocarbons (PAHs)
• 9-hydroxyphenanthrene
• carbon-13
• internal standard
• stable isotope labeling

Acknowledgments

The authors would like to thank Marie-Claude Trottier (CRCHU de Québec-UL) and Pierre Dumas (INSPQ) for analytical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the Center de Toxicologie du Québec (CTQ), Institut national de santé publique du Québec (INSPQ).