Identification of some human urinary metabolites of orally administered potassium canrenoate by stable isotope-labeling techniques.
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A single oral dose (200 mg) of an equimolar mixture of potassium canrenoate and its 20,20,21,21-tetradeutero analogue was administered to three healthy men. The steroids in urine collected for 24 hr after dosage were isolated on XAD-2 resin, and purified and fractionated into groups by lipophilic gel chromatography before and after hydrolysis of conjugates. GC/MS analysis of these fractions allowed the detection and identification of canrenone, canrenoic acid and its ester glucuronide, 3 beta-hydroxy-3-deoxocanrenone, 3beta-hydroxy-4,5alpha-dihydro-3-deoxocanrenone and a 3epsilon-hydroxy-4,5,6,7-tetrahydro-3-deoxocanrenone. In addition a number of di- and trihydroxy compounds formed by reduction and hydroxylation were partially identified from their E1 and C1 mass spectra. The results provide information on the metabolism of oral potassium canrenoate in man, and demonstrate the utility of combining stable isotope labeling, lipophilic gel chromatography, and GC/MS in studies of steroidal spirolactones.
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