Sulfamate formation is a major route for detoxification of 2-amino-3-methylimidazo[4,5-f]quinoline in the rat

Abstract

The major biliary metabolite of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the rat was identified as the sulfamate derivative, N-[3-methylimidazo[4,5-f]quinolin-2-yl] sulfamic acid. Identification was accomplished primarily by u.v., 1H-n.m.r. and mass spectrometry of the material isolated from bile and confirmed by comparison with material synthesized by reaction of chlorosulfonic acid with IQ. The sulfamate was shown to be non-mutagenic in bacterial forward mutation assays. Greater than 20% of an administered dose of IQ could be recovered from feces (17%) and urine (5%) as the sulfamate. Very little unmetabolized IQ was recovered in bile, urine, or feces. Thus, the unusual process of N-sulfation is a major contributor to the detoxification and elimination of IQ in the rat.