SPECTRAL AND CHROMATOGRAPHIC PROPERTIES OF 2-METHOXYPHENYLMETYRAPONE AND ITS POTENTIAL METABOLITES

In the search for new metyrapone derivatives as radioligands for the f unctional diagnosis of adrenal pathology, 2-methoxyphenylmetyrapone me thoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone] (1), and related 2-su bstituted phenylmetyrapone derivatives, have been separated as potent inhibitors of adrenal 11 beta-hydroxylase, with high affinity for adre nal mitochondrial binding sites. Surprisingly, 2-[C-11]MPMP showed a r apid loss of the radioactive label, which prompted investigation of it s metabolism. Synthetic 2-MPMP (1) and its seven potential metabolites (2-8) have been identified spectroscopically (H-1- and C-13-NMR and m ass spectrometry) and further characterised by chromatography (TLC and gradient reversed-phase HPLC). Chromatographic and mass analysis of u rinary extracts from rats dosed with 2-MPMP have confirmed the major m etabolites as 2-hydroxyphenylmetyrapone(2-OHPMP), 2) and its N-oxide ( 2-OHPMP-NO, 6), which are present predominantly as conjugates.