Abstrakt: |
Electron impact mass spectral studies on the mono-and di-N-oxides of metyrapone and metyrapol revealed that the technique readily differentiates between the mono-N-oxides of metyrapol, but not of metyrapone. The unequivocal mass spectral differentiation between the isomeric N-oxide metabolites of metyrapone was achieved by the selective and rapid reduction of the keto group in these compounds, with sodium borohydride, to yield the correspoding metyrapol-N-oxides. Chromatographic methods (thin-layer chromatography, gas-liquid chromatography and high-performance liquid chromatography) have been developed for the separation and identification of potential in vitrometabolites of metyrapone. Incubation of metyrapone, under oxidative conditions, with rat or mouse hepatic microsomal preparations, afforded metyrapol (keto reduction) and the isomeric mono-N-oxides of metyrapone. Similar incubation with the hepatic soluble fraction yielded, in addition to metyrapol, an a-pyridone metabolite. |