%0 Journal Article %A J De Graeve %A J E Gielen %A G F Kahl %A K H Tüttenberg %A R Kahl %A B Maume %T Formation of two metyrapone N-oxides by rat liver microsomes. %D 1979 %J Drug Metabolism and Disposition %P 166-170 %V 7 %N 3 %X In the presence of phenobarbital-pretreated rat liver microsomes and under oxidative conditions, metyrapone is transformed in vitro into reduced metyrapone and two other metabolites. In an effort to further characterize those metabolites, large-scale incubations of metyrapone were performed. Untransformed substrate and metabolites were extracted into chloroform under alkaline conditions and separated by thin-layer chromatography. The nature of the metabolites as N-oxides located on either pyridine ring was established by physical methodologies, mainly electron-impact and chemical-ionization mass spectrometry, and also by chemical reactions with titanous chloride. The formation of both N-oxides was increased in microsomes from phenobarbital-, but not from 3-methylcholanthrene-pretreated animals. N-Oxide formation during metyrapone metabolism might be an important step in its inhibitory action on the cytochrome P-450-mediated drug metabolism. %U https://dmd.aspetjournals.org/content/dmd/7/3/166.full.pdf