Biotransformation of 1,8-cineole in the brushtail possum (Trichosurus vulpecula).

1. The metabolic fate of 1,8-cineole was investigated in the brushtail possum. Six possums were fed an artificial diet to which 0.5% 1,8-cineole (wet weight) was added for 2 days. Urine and faeces were collected after the second day. A sample of each was extracted into ethyl acetate and analysed for metabolites. Both free and total levels of metabolites were identified by GC-MS and LC-MS and quantified by GC-MS. 2. The pattern of metabolite excretion was very complex in the brushtail possum. Nineteen metabolites were found in total. Metabolites were categorized into four groups according to the oxidation they had undergone: hydroxycineoles (n = 3), cineolic acids (n = 2), dihydroxycineoles (n = 3) and hydroxycineolic acids (n = 11). No hydroxycineolic acid metabolites have been previously reported as metabolites of 1,8-cineole. 3. Fractional recovery of the ingested dose (2.4 +/- 0.5 g; mean +/- SD) was 0.44 +/- 0.14 (mean +/- SD) in 24 h. Sixty percent of excreted metabolites were hydroxycineolic acids, the most extensively oxidized metabolites. Conjugation with glucuronic acid was inversely related to metabolite polarity, being greatest for hydroxycineoles (41-82%) and minimal for hydroxycineolic acids. 4. Traces of most metabolites were also found in the faeces.