Carcinogenic N-nitrosodimethylamine as a contamination in drugs containing 4-dimethylamino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (amidopyrine, aminophenazone)

Abstract

A total of 68 commercially available drugs containing amidopyrine were investigated for contamination with the strong carcinogen N-nitrosodimethylamine (NDMA). All samples contained varying amounts of NDMA. About half of the drugs contained 1--10 micrograms/kg, 40% contained 11--50 micrograms/kg, 7% contained 51--10 micrograms/kg and one sample had 370 micrograms/kg. NDMA-contents in batches of pure amidopyrine that had been utilized for preparation of drugs were higher than those in the respective drugs: about one-third was in the range of 20--50 micrograms/kg, one-third had 51--100 micrograms/kg, and one-third was above 100 micrograms/kg. There was, however, no correlation between NDMA-contents of batches of the pure substance and NDMA-contents of the drugs prepared from these batched. NDMA concentrations in the samples were inhomogenously distributed. It could be demonstrated that amidopyrine in substance reacts extremely rapidly with nitrogen oxides from the air to form NDMA. Ascorbic acid, which prevents nitrosamine formation in aqueous-acidic solution, under these conditions had no protective effect.