Identification of urinary metabolites of orally administered N,N-dimethyl-p-toluidine in male F344 rats.
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.
Kim
Nam-Cheol
NC
Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
Ghanbari
Katayoon
K
Kracko
Dean A
DA
Weber
Waylon M
WM
McDonald
Jacob D
JD
Dix
Kelly J
KJ
D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011916:Rats, Inbred F344; D014052:Toluidines / Q000008:administration & dosage / Q000652:urine*
D002250:Carbon Radioisotopes; D014052:Toluidines; C015835:dimethyl-4-toluidine