Identification by proton NMR of N-(hydroxymethyl)-N-methylformamide as the major urinary metabolite of N, N-dimethylformamide in mice

Abstract

Urine samples from mice which had received N,N-dimethylformamide were investigated by high field 1H-NMR spectroscopy. The most prominent signals in the N-CH 3 region had chemical shifts identical with those of N,N-dimethylformamide ( δ 2.85, 3.01) and N- (hydroxymethyl)-N-methylformamide ( δ 2.91, 3.05). Resonances downfield of δ7.5 (from formyl protons) also coincided with those of the reference formamides. When [ 14C]methyl-labelled, N,N-dimethyl-formamide was injected and urine samples investigated by radio thin layer chromatography, the major area of radioactivity corresponded to the Rf of N-(hydroxymethyl)-N-methylformamide. Dimethylamine and methylamine were found to be minor metabolites of N,N-dimethyl-formamide.