Isolation and identification of spirorenone metabolites from the monkey (Macaca fascicularis).

The plasma level of spirorenone was determined 3 h after 1, 8, 22 and 46 daily oral administrations of 20 mg/kg to two female and two male monkeys (Macaca fascicularis). A fifth animal, female, was treated with eight daily doses of tritium-labelled drug and was completely bled from the carotid vein 4 h after the last administration in order to isolate and identify plasma metabolites. After repeated daily doses of spirorenone the mean plasma level of unchanged drug was 711 +/- 213 ng/ml. In the plasma of the fifth animal four radioactively labelled compounds could be detected after extraction and subsequent HPLC separation. Mass spectrometric identification of three of the substances indicated 1,2-dihydrospirorenone, hydroxy-1,2-dihydrospirorenone and the unchanged drug itself.