Oxidative metabolism of hydralazine. Evidence for nitrogen centered radicals formation

The oxidative metabolism of hydralazine, a hydrazine-containing hypotensive drug, has been studied using a spin-trapping technique. In the presence of Cu²⁺, Fe²⁺ and Fe³⁺, hydralazine rapidly forms a nitrogen-centered-DMPO adduct with a^N = 15.0G, a_β^H = 16.7G and a_β^N = 2.55G. While catalase has a very small inhibitory effect, superoxide dismutase completely inhibits the formation of the DMPO adduct. Mass spectral analysis of the adduct indicates that the hydralazyl radical is trapped with DMPO. Human red blood cells also catalyze the formation of a nitrogen-centered-DMPO adduct, a^N = 15.9G, a_β^H = 19.4G and a_β^N = 1.7G, which is different than that obtained with metal ions. DMPO-H adduct is also formed in the red cells from hydralazine.