Nitrosation of orally administered drugs under simulated stomach conditions.

Of a total of 61 drugs considered to be potentially nitrosatable on the basis of their chemical structure, 7 have indeed been nitrosated in gastric juice at pH 2 and under simulated human stomach conditions, where the pH was varied from about 7 to 2 within 60 min. The 7 nitrosatable drugs were ethambutole, despiramine hydrochloride, clomipramine hydrochloride, phenoxymethyl penicillin, aminophenazone, piperazine diadipate and analgine. Inhibition of nitrosation under simulated stomach conditions was also investigated using ascorbic acid, sulfanilamide, p-aminosalicylic acid and sulfamic acid. The first three agents were effective inhibitors, whereas sulfamic acid stimulated nitrosation within a distinct pH range.