Identification of Mutagenic Nitrosation Products of Antipyrine and Evaluation of Their Formation under Model Stomach Conditions

Nitrosation products of antipyrine treated with nitrite under the conditions recommended by the WHO were examined. An unknown product was confirmed to be formed besides 4-nitrosoantipyrine (a known nitrosation product), and was isolated and identified as 1-(2-hydroxyimino-3-oxobutyryl)-2-methyl-2-nitroso-1-phenylhydrazine.This new nitrosation product showed mutagenicity to Salmonella typhimurium TA 98 and TA 100 either with or without S9 mix. Model experiments indicated that antipyrine is probably easily nitrosated in the stomach after administration to give these nitrosation products.