RT Journal Article SR Electronic T1 METABOLISM OF DEBRISOQUINE SULFATE JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 332 OP 337 VO 3 IS 5 A1 J. G. ALLEN A1 P. B. EAST A1 R. J. FRANCIS A1 J. L. HAIGH YR 1975 UL http://dmd.aspetjournals.org/content/3/5/332.abstract AB 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. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics