Identification of novel hydrazine metabolites by 15N-NMR.
15N-NMR has been used to study the metabolism of hydrazine in rats in vivo. Single doses of [15N2]hydrazine (2.0 mmol/kg: 98.6% g atom) were administered to rats and urine collected for 24 hr over ice. A number of metabolites were detected by 15N-NMR analysis of lyophilized urine. Ammonia was detected as a singlet at 0 ppm and unchanged [15N2]hydrazine was present in the urine detectable as a singlet at 32 ppm. Peaks were observed at 107 and 110 ppm which were identified as being due to the hydrazido nitrogen of acetylhydrazine and diacetylhydrazine, respectively. A resonance at 85 ppm was ascribed to carbazic acid, resulting from reaction of hydrazine with carbon dioxide. A singlet detected at 316 ppm was thought to be due to the hydrazono nitrogen of the pyruvate hydrazone. The resonance at 56 ppm was assigned to 15N-enriched urea, this together with the presence of ammonia indicates that the N-N bond of hydrazine is cleaved in vivo, possibly by N-oxidation, and the resultant ammonia is incorporated into urea. A doublet centred at 150 ppm and a singlet at 294 ppm were assigned to a metabolite which results from cyclization of the 2-oxoglutarate hydrazone. Therefore 15N-NMR spectroscopic analysis of urine has yielded significant new information on the metabolism of hydrazine.
Preece
N E
NE
Toxicology Unit, School of Pharmacy, University of London, U.K.
Nicholson
J K
JK
Timbrell
J A
JA
D000641:Ammonia / Q000652:urine; D000818:Animals; D006834:Hydrazines / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006834:Hydrazines; C029424:hydrazine; D000641:Ammonia; C014949:acetylhydrazine