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

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.