Synthesis, in vitro reactivity, and identification of 6-phenyl-3-hexen-2-one in human urine after kava-kava (Piper methysticum) ingestion

Abstract This study describes the synthesis of 6 -phenyl-3-hexen-2-one, a proposed metabolite of kava-kava (kava, ‘Awa, Yaqona, PIPER METHYsTICUM Forst.), its reactivity with glutathione IN VITRO, and its isolation and identification, as its mercapturic acid adduct using LC/MS/MS, in the urine of two human subjects following their ingestion of kava. A possible metabolic pathway for the formation of this metabolite and its possible role in hepatotoxicity are also discussed.