Metabolism of 1,2-dimethylhydrazine in isolated perfused rat liver

The metabolism of 1,2-dimethylhydrazine (DMH) was investigated in isolated perfused rat liver. The separation of [14C]DMH and its metabolites azomethane (AM), azoxymethane (AOM) and methylazoxymethanol (MAM) was performed by high pressure liquid chromatography (HPLC). The fractions were quantitatively detected by liquid scintillation counting of the radioactivity. It was demonstrated that DMH is highly metabolized by the liver. After 1 h of perfusion, the median amounts of DMH and its metabolites in the medium were: DMH, 16%; AM, 3%; AOM, 42%; MAM, 30% of the given dose. During this time 9.9% and 0.7% of the total radioactivity were eliminated as AM and CO2 in the oxygen stream of the perfusion apparatus; 0.6% were excreted by bile and 12.3% stored in hepatic tissue. The reaction rate (t1/2) of each individual metabolic step was estimated by means of a mathematical kinetic model as follows: DMH leads to AM, 21.8 min; AM leads to AOM, 1.5 min; AOM leads to MAM, 41.5 min; MAM leads to, 611 min. The results are discussed in comparison to in vivo experiments.