Mechanism of decomposition of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen.

ABSTRACT

The decomposition of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 2), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 1) in aqueous solution is quantitatively accounted for by the appearance of equimolar amounts of p-nitrosophenol and acetaminophen. The rate of decomposition depends on initial concentration and varies with pH. Antioxidants decrease the rate of decomposition and change the products. In the presence of cysteine, N-acetyl-3-(S-cysteine)-p-aminophenol, an in vivo metabolite of acetaminophen, is a product of decomposition.