Identification of urinary metabolites of orally administered N,N-dimethyl-p-toluidine in male F344 rats

J Toxicol Environ Health A. 2007 May 15;70(10):781-8. doi: 10.1080/15287390701206176.


The metabolism of orally administered N,N-dimethyl-p-toluidine (DMPT) in male F344 rats was investigated. The rat urinary metabolite profile was determined by analytical reverse-phase high performance liquid chromatography (HPLC). Four radiolabeled peaks were observed, isolated, and purified by solid-phase extraction (SPE) and preparative HPLC methods. The 4 peaks were identified as p-(N-acetylhydroxyamino)hippuric acid (M1), DMPT N-oxide (M2), N-methyl-p-toluidine (M3), and parent DMPT. Metabolites M1 and M2 were identified by spectrometric and spectroscopic methods, including mass fragmentation pattern identification from both liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry, and from chemical analysis of nuclear magnetic resonance spectra. Structural confirmation of metabolite M2 was accomplished by comparison with a synthetic standard. Peaks M3 and the peak suspected to be DMPT were identified by comparison of their HPLC retention times and mass fragmentation patterns with authentic standards of N-methyl-p-toluidine and DMPT, respectively. DMPT metabolism is similar to that reported for N,N-dimethylaniline.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Carbon Radioisotopes
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Rats
  • Rats, Inbred F344
  • Toluidines / administration & dosage
  • Toluidines / urine*


  • Carbon Radioisotopes
  • Toluidines
  • dimethyl-4-toluidine