Reaction of Drugs with Sodium Nitroprusside as a Source of Nitrosamines

Potentially dangerous nitrosamines have been shown to result from the reaction of sodium nitrogusside with several drugs under physiological conditions (pH 7.3 and $37^\circ{C})$. In each case the products were identical to those produced upon reaction with nitrous acid at much lower pH values. Reaction rates were shown to reflect a first order dependence on both amine and nitroprusside concentrations and to increase at higher pH values, approximately in proportion to concentrations of unprotonated amine. Fast reactions of sodium nitroprusside with reduced glutathione, cysteine, and ascorbate suppress but do not prevent the conversion of amines into N-nitrosamines. These results show sodium nitroprusside to be very potent nitrosating agent under physiological conditions and suggested nitrosamines may be formed during its normal pharmacological administration.