Spironolactone metabolism in man studied by gas chromatography-mass spectrometry.
Gas chromatography-mass spectrometry was used to identify metabolites of spironolactone in human blood and urine. In three healthy men about 20% of the radioactivity was excreted in the urine within 24 hr after an oral dose of [20-3H]spironolactone (200 mg + 200 muCi). About half of this radioactivity was extracted with chloroform at pH 3 and from this extract four stable metabolites were isolated by use of column and thin-layer chromatography. Two of these were the previously identified metabolites, canrenone (VII; 2.9% of dose) and the 6beta-hydroxy-sulfoxide (X; 1.8% of the dose). The remaining were the new metabolites, 15alpha-hydroxycanrenone (XI; 0.8% of dose) and the 6beta-hydroxy-thiomethyl derivatives (VI; 0.5% of dose). The principal water-soluble urinary metabolite was canrenoate ester glucuronide (XII; 4.5% of dose). In the 24- to 32-hr pooled serum, canrenone (VII) was the principal metabolite in the organic-extractable fraction; VI was present in appreciable amounts but X and XI were present at extremely low levels.
D002192:Canrenone / Q000032:analysis; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D013148:Spironolactone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013438:Sulfhydryl Compounds / Q000032:analysis; D013454:Sulfoxides / Q000032:analysis
D013438:Sulfhydryl Compounds; D013454:Sulfoxides; D013148:Spironolactone; D002192:Canrenone