Quantification of α-Thujone and Its Metabolites in Human Urine after Consumption of a Sage Infusion Using Stable Isotope Dilution Assays.

The metabolism of the monoterpene α-thujone was investigated in humans after consumption of sage tea, by analyses of its metabolites 2-hydroxythujone, 4-hydroxythujone, and 7-hydroxythujone in urine. For the quantitation of α-thujone and its metabolites, stable isotope dilution assays were developed. Using ₆-α-thujone as internal standard, we quantified α-thujone by solid phase microextraction GC-MS and the hydroxythujones with ₆-2-hydroxythujone, ₆-4-hydroxythujone, and ₆-7-hydroxythujone after glucuronide/sulfate deconjugation by LC-MS/MS in urine.

A six-step total synthesis of α-thujone and d-α-thujone, enabling facile access to isotopically labelled metabolites.

The short synthesis of α-thujone relies on the functionalization of the readily available dimethylfulvene. Furthermore, the three main metabolites of the natural product were also synthesized. Since d-acetone can be used as a starting material, the route developed allows for the facile incorporation of isotopic labels which are required for detecting and quantifying trace amounts via GC/MS analysis.