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

1. The metabolic fate of 1,8-cineole was investigated in the brushtail poss um. 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 se cond day. A sample of each was extracted into ethyl acetate and analysed fo r 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 po ssum. Nineteen metabolites were found in total, Metabolites were categorize d into four groups according to the oxidation they had undergone: hydroxyci neoles (n = 3), cineolic acids (n = 2)1 dihydroxycineoles (n = 3)and hydrox ycineolic acids (n = 11). No hydroxycineolic acid metabolites have been pre viously reported as metabolites of 1,8-cineole. 3. Fractional recovery of the ingested dose (2.4 +/- 0.5 g; mean +/- SD) wa s 0.44 +/- 0.14 (mean +/- SD) in 24 h. Sixty percent of excreted metabolite s were hydroxycineolic acids, the most extensively oxidized metabolites. Co njugation with glucuronic acid was inversely related to metabolite polarity , being greatest for hydroxycineoles (41-82 %) and minimal for hydroxycineo lic acids. 4. Traces of most metabolites were also found in the faeces.