Identification of some human urinary metabolites of the intoxicating beverage kava.

Methane chemical ionization (CI) gas chromatography-mass spectrometry (GC-MS) has been used to identify some of the human urinary metabolites of the kava lactones following ingestion of kava prepared by the traditional method of aqueous extraction of Piper methysticum. All seven major, and several minor, kava lactones were identified in human urine. Observed metabolic transformations include the reduction of the 3,4-double bond and/or demethylation of the 4-methoxyl group of the alpha-pyrone ring system. Demethylation of the 12-methoxy substituent in yangonin (or alternatively hydroxylation at C-12 of desmethoxyyangonin) was also recognised. This product was isolated by high-performance liquid chromatographic analysis of crude urine extracts and characterised by methane CI GC-MS. In contrast to the situation prevailing in the rat no dihydroxylated metabolites of the kava lactones, or products from ring opening of the 2-pyrone ring system, were identified in human urine. GC-MS analysis of urine can be readily utilised to determine whether donors have recently consumed kava.

Uptake into mouse brain of four compounds present in the psychoactive beverage kava.

A technique using gas chromatography-mass spectrometry and deuterated internal standards is described for the quantitation in brain tissue of four constituents of the intoxicating beverage kava. Dihydrokawain, kawain, desmethoxyyangonin, and yangonin were administered ip to mice at a dosage of 100 mg/kg. At specific time intervals (5, 15, 30, and 45 min), the mice were sacrificed and the brain concentrations of these four compounds determined. After 5 min, dihydrokawain and kawain attained maximum concentrations of 64.7 +/- 13.1 and 29.3 +/- 0.8 ng/mg wet brain tissue, respectively, and were rapidly eliminated. In contrast, desmethoxyyangonin and yangonin had poorly defined maxima corresponding to concentrations of 10.4 +/- 1.5 and 1.2 +/- 0.3 ng/mg wet brain tissue, respectively, and these compounds were more slowly eliminated from brain tissue. When crude kava resin was administered ip at a dosage of 120 mg/kg, the concentration in brain of kawain and yangonin markedly increased (2 and 20 times, respectively) relative to the values measured from their individual injection. In contrast, dihydrokawain and desmethoxyyangonin, after the administration of crude resin, remained at the percentage incorporation into brain tissue established for their individual ip injection.

Identification by methane chemical ionization gas chromatography/mass spectrometry of the products obtained by steam distillation and aqueous acid extraction of commercial Piper methysticum.

Bornyl cinnamate has been identified as a constituent of kava resin and of the steam distillate of Piper methysticum. 5-Hydroxydihydrokawain was identified in commercial samples of P. methysticum originating from Vanuatu provided an initial aqueous extraction was employed. Commercial preparations, and fresh samples of the root of this plant from Fiji, lacked this compound. Two previously described N-cinnamoyl pyrrolidine alkaloids were also observed along with stigmasterol in kava resin from Fiji and Vanuatu. The products derived from aqueous 2 M hydrochloric acid extraction of P. methysticum were determined from methane chemical ionization gas chromatography/mass spectrometry analysis which identified a series of hydroxylated compounds (15a-d) derived from formal decarbonylation of the parent kava lactones. The products (13a-c) of dehydration of these compounds were also observed. The efficiency of kava resin extraction from plant material by water (the traditional method of preparation of the kava beverage) was typically 5-10% of that recovered by direct extraction with an organic solvent.