Reaction of drugs with nitrous acid as a source of carcinogenic nitrosamines.

Twelve common drugs that are tertiary amines react with nitrite in aqueous solution at ph 3 to 4 to form dialkylnitrosamines that are known carcinogens. Aminopyrine gave dimethylnitrosamine in 30% yield or higher at all concentra tions down to 50 ppm (with 25 ppm nitrite); the other product of this reaction was the nitrite salt of 4-hydroxyantipyrine. The other drugs, when present at 0.01 Mwith 0.04 Mnitrite, formed nitrosamines in yields ranging from 0.03% from dextropropoxyphene to 2.4% from lucanthorre in 4 hr at 37°.