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Xenobiotica
the fate of foreign compounds in biological systems
Volume 23, 1993 - Issue 6
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Research Article

Identification of four biliary metabolites of the diterpene sclareol in the laboratory rat

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Pages 621-632 | Received 22 Jan 1992, Accepted 12 Mar 1993, Published online: 22 Sep 2008
 

Abstract

1. Ag.l.c. method was developed to determine sclareol (1) and its microbial metabolites: 3-keto-sclareol (2), 2α;-hydroxysclareol (3), 3α;-hydroxysclareol (4), 3β-hydroxysclareol (5), 18-hydroxysclareol (6), and 2α;, 18-dihydroxysclareol (7) in both microbial cultures and biological fluids of the laboratory rat.

2. Metabolism of the diterpene (1) was studied in the laboratory rat. This in vivo study was facilitated by the availability of microbial metabolites of sclareol as reference standards, and the g.l.c. assay for sclareol and its metabolites in biological fluids.

3. Following i.v. treatment (100 mg/kg), the disappearance of (1) from rat plasma was rapid and biphasic. No microbial metabolites of sclareol were detectable in plasma.

4. Sclareol (1) and its microbial metabolites were not detected in rat urine following either i.v. or oral treatments; unchanged (1) was excreted in rat 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 biliary metabolites of (1) (0.4% dose) were identified as (2), and (4)-(6) based on g.l.c.-mass spectrometry and comparisons with reference standards. All four biliary metabolites of (1) in rat have been identified as microbial metabolites of (1).

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