The fate of N-methylformamide in mice. Routes of elimination and characterization of metabolites.

The fate of N-methylformamide has been investigated in male CBA/CA mice following the administration of this compound labeled with 14C either in the methyl or in the formyl group. The major route of elimination was found to be via the kidneys although a substantial quantity (39% of the dose) was eliminated via the lungs as CO2 in the case of [14C]formyl-labeled N-methylformamide. In addition to the unchanged compound three metabolites were found in the urine by TLC autoradiography. One of these metabolites was identified as methylamine after conversion to its 2,4-dinitrophenyl derivative. The derivative was isolated and shown to be N-methyl-2,4-dinitroaniline by mass spectrometry. Further evidence that methylamine was a metabolite of N-methylformamide was provided by ion pair HPLC analysis of urine from mice dosed with [14C]methyl-labeled N-methylformamide. The second metabolite was tentatively identified as N-hydroxymethylformamide which was present in the urine of mice dosed with either [14C]methyl- or [14C]formyl-labeled N-methylformamide. Formate was not a urinary metabolite of N-methylformamide. The identity of the third urinary metabolite remains unknown.