Formation of N-acetyl-p-benzoquinone imine, the well-known toxic metabolite of acetaminophen, by the reaction of acetaminophen with nitrite under model stomach conditions.

Abstract

The main reaction product of acetaminophen (4mM) with nitrite (1mM) under model stomach conditions was identified as p-benzoquinone. HPLC analysis of the reaction mixture with an electrochemical detector revealed the presence of N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen, as an intermediate in p-benzoquinone formation. About 14% of acetaminophen was estimated to be transformed into this intermediate when the reaction was carried out at pH 3 for 1 h at 37°C.