EVIDENCE FOR THE INVOLVEMENT OF N-ACETYL-P-QUINONEIMINE IN ACETAMINOPHEN METABOLISM

Evidence of the presence of N-acetyl-p-quinoneimine (NAPQI), a postulated toxic intermediate of acetaminophen [an analgesic] metabolism, in mouse liver microsomal incubations is reported. The intermediate was tentatively identified by comparison with synthetic NAPQI generated electrochemically from acetaminophen in a coulometric flow reactor. All but 1 of the reaction products of NAPQI with a number of nucleophiles were found in vitro as well, and in similar relative amounts. The NAPQI intermediate is moderately stable at physiological pH and temperature with a lifetime which is dependent on the components of the medium.