IDENTIFICATION OF 4 BILIARY METABOLITES OF THE DITERPENE SCLAREOL IN THE LABORATORY RAT

1. A g.l.c. method was developed to determine sclareol (1) and its mic robial metabolites: 3-keto-sclareol (2), 2alpha-hydroxysclareol (3), 3 alpha-hydroxysclareol (4), 3beta-hydroxysclareol (5),18-hydroxysclareo l (6), and 2alpha, 18-dihydroxysclareol (7) in both microbial cultures and biological fluids of the laboratory rat. 2. Metabolism of the dit erpene (1) was studied in the laboratory rat. This in vivo study was f acilitated by the availability of microbial metabolites of sclareol as reference standards, and the g.l.c. assay for sclareol and its metabo lites in biological fluids. 3. Following i.v. treatment (1 00 mg/kg), the disappearance of (1) from rat plasma was rapid and biphasic. No mi crobial metabolites of sclareol were detectable in plasma. 4. Sclareol (1) and its microbial metabolites were not detected in rat urine foll owing either i.v. or oral treatments; unchanged (1) was excreted in ra t faeces to the extent of 9% of an oral dose in 48 h. 5. Following i.v . treatment, 0.02% dose was recovered in bile as unchanged (1). Four b iliary metabolites of (1) (0.4% dose) were identified as (2), and (4)- (6) based on g.l.c.-mass spectrometry and comparisons with reference s tandards. All four biliary metabolites of (1) in rat have been identif ied as microbial metabolites of (1).