Proton NMR spectroscopic studies on the metabolism and biochemical effects of hydrazine in vivo.

The metabolism and disposition of hydrazine and its effects on endogenous metabolites has been studied in rats by the use of high resolution proton NMR spectroscopy of urine. Several metabolites of hydrazine were detected, notably acetyl- and diacetylhydrazine and a cyclised metabolite which results from a hydrazone formed from 2-oxoglutarate and hydrazine. Effects of hydrazine on endogenous metabolites in urine and plasma were also observed; notably a dose-related increase in urinary taurine, a dose-related increase in urinary and plasma lactate, increases in urinary alpha-alanine, beta-alanine, methylamine and a decrease in urinary 2-oxoglutarate.

Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat.

Deuterium labeling techniques and stereoselective GC/MS methodology have been employed to investigate the mechanism by which R-ibuprofen undergoes metabolic chiral inversion in the rat in vivo. Following oral administration of a mixture of R-ibuprofen (7.5 mg kg-1) and R-[ring-2H4; 2-2H]ibuprofen (R-[2H5]ibuprofen) (7.

Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data.

A computer-based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi-dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra.

Studies on the metabolism and chiral inversion of ibuprofen in isolated rat hepatocytes.

The oxidative metabolism and chiral inversion of ibuprofen in freshly isolated rat hepatocytes was studied with the aid of a stereoselective GC/MS assay procedure. Hydroxylation of the isobutyl side chain at the subterminal carbon (to give hydroxyibuprofen) proved to be the major route of metabolism of both R(-)-ibuprofen and S(+)-ibuprofen, while formation of the corresponding diastereoisomeric 2-methylpropionic acid derivatives (carboxyibuprofen) was of minor quantitative importance. Both oxidative pathways were inhibited in the presence of metyrapone, a cytochrome P-450 inhibitor.

Hepatotoxin-induced hypertaurinuria: a proton NMR study.

The urinary excretion of taurine by rats after dosing with various hepatotoxins has been investigated by 1H NMR spectroscopy. After single hepatotoxic doses of hydrazine, carbon tetrachloride, 1-naphthylisothiocyanate, or thioacetamide there was biochemical and histopathological evidence of hepatic damage. Proton NMR spectroscopy of the urine collected for 24 h after dosing from these animals revealed a marked elevation in taurine (control 11.