Abstract

Major urinary metabolites in man of 6-amino-2-fluoromethyl-3-(o-tolyl)-4-(3H)-quinazolinone (afloqualone, I), a new centrally acting muscle relaxant, were identified by GC/MS. Simultaneous quantitative determination of the metabolites was made by mass chromatography using deuterium-labeled internal standards. Approximately 4% of the dose was excreted as unchanged I within 32 hr after oral administration. The major metabolites identified in the neutral and basic fractions of the urine were N-acetylafloqualone (II, 0.3% of the dose), N-acetyl-2'-hydroxymethylafloqualone (III, 5.5%), N-glycolylafloqualone (IV, 0.9%), and N-glycolyl-2'-hydroxy-methylafloqualone (V, 1.3%). I and IV were also excreted in conjugated form as N-glucuronide (VI, 8.0%) and O-glucuronide and/or sulfate (VII, 0.4%), respectively. Other phenolic and sulfur-containing metabolites of I, which have previously been identified in the urine of rats, dogs, or monkeys, were not detected in the human urine. Thus, the main routes of metabolism of I in man consist of N-acetylation followed by hydroxylation at the 2'-methyl and acetylmethyl carbons, and glucuronidation of the aromatic amino group. This pattern of metabolism of I in man was in part similar to that observed in rats and monkeys, but drastically different from that in dogs.