Nitrosation of drugs under in-vivo conditions

Application of the WHO Nitrosation Assay Procedure (NAP test) to a range of potentially nitrosatable drugs has given rise to considerable variations in the formation of volatile N-nitrosamines and N-nitroso compounds as a group. No nitrosation whatsoever was observed with 40 mM nitrite in some instances. In simulating more closely the conditions likely to be encountered in the human stomach, however, the order of susceptibility of the drugs to N-nitrosation has proved to be very different. At a constant nitrite concentration of 25 microM, which is considered to represent the upper limit of those likely to be encountered in the acidic human stomach, the drugs giving rise to the greatest yields of products reacting as N-nitroso compounds from a maximum adult dose were the penicillins, G, V, cloxacillin and ampicillin.