ABSTRACT
When 6-chloro-9β,10α-pregna-1,4,6-triene-3,20-dione (trengestone) was incubated with liver slices of male rats, the substrate was rapidly transformed to a polar metabolite; in contrast, liver slices of female rats metabolised trengestone much more slowly, and only traces of a polar metabolite could be detected. After paper and thin layer chromatography in various systems, the polar metabolite was obtained in crystalline form and identified as 6-chloro-16α-hydroxy-9β,10α-pregna-1,4,6-treiene-3,20-dione (16α-hydroxytreengestone) by its infrared spectrum and by gas chromatography-mass spectrometry. After administration of trengestone to male or female rats, the main metabolite in the urine was again a6α-hydroxytrengestone.
When trengestone was incubated with liver slices of male or female human subjects, two metabolites were detected, one of which was formed in large amounts. By comparison with the authentic compound, the major metabolite proved to be identical with (20S)-6-chloro-20-hydroxy-9β,10α-pregna-1,4,6-triene-3-one (20α-hydroxytrengestone). After oral administration of radioactive trengestone to man, the amount of total radioactivity in the urine was considerably greater in a human female (50 %) than in two human males (6–8 %). The main metabolite of trengestone was identified as 20α-hydroxytrengestone.
When trengestone was given orally to a female rabbit, and to a female Rhesus monkey, both the 20α-hydroxy and the 2β-hydroxy derivatives of trengestone were detected in the urine. These experiments demonstrate considerable differences in the metabolism of the rat, rabbit, monkey, and man.
Authentic compound-free strategy for simultaneous determination of primary coumarins in Peucedani Radix using offline high performance liquid chromatography–nuclear magnetic resonance spectroscopy–tandem mass spectrometry
