Metabolism of debrisoquine sulfate. Identification of some urinary metabolites in rat and man.
A high proportion of an oral dose of 14C-debrisoquine sulfate is excreted in the urine by rat and man. The urinary radioactivity consists of a mixture of unchanged drug and polar, water-soluble metabolites which cannot be extracted into organic solvents. Treatment of methanolic extracts of the freeze dried urine with acetylacetone incorporates the amidino group of debrisoquine and these metabolites into a 4,6-dimethylpyrimidine ring, and yields derivatives which can be readily extracted from aqueous solution. Gas-liquid chromatographic-mass spectrometric studies of these extracts have shown that in both species: 1) the major metabolite is formed by 4-hydroxylation of debrisoquine; 2) a significant proportion of the dose is excreted as acidic metabolites, formed by opening the tetrahydroisoquinoline ring; 3) trace amounts of phenolic metabolites (5-, 6-, 7-, and 8-hydroxydebrisoquines) are also excreted.
D000818:Animals; D002849:Chromatography, Gas; D003647:Debrisoquin / Q000652:urine*; D005612:Freeze Drying; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats
D007546:Isoquinolines; D003647:Debrisoquin