URINARY METABOLIC PROFILE IN RAT OF -METHOXYPHENYL)-2-METHYL-2-(3-PYRIDYL)-1-PROPANONE - A POTENTIAL RADIOLIGAND FOR FUNCTIONAL DIAGNOSIS OF ADRENAL PATHOLOGY

1. The metabolism of -methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanon e (2-MPMP) was studied in the male Sprague-Dawley rat after 50 mg/kg, i.v. dose. 2. Organic solvent extracts of urine samples were directly analysed by reversed-phase gradient hplc. The identified metabolites w ere also isolated by preparative tie, and analyzed by direct probe mas s spectrometry. In the case of conjugated metabolites, the urine sampl es were deconjugated by enzyme hydrolysis prior to extraction. The str uctures of metabolites were confirmed by comparison of their chromatog raphic behaviours, UV spectra, and mass spectra with those of authenti c standards. 3. The metabolites identified in the 0-24-h urine samples were 2-hydroxyphenylmetyrapone (2-OHPMP) and 2-hydroyphenylmetyrapone N-oxide (2-OHPMP-NO), which were present predominantly as their glucu ronide and/or sulphate conjugates. 4. 2-MPMP and four of its metabolit es present in the 0-24-h urine samples were quantified by a reversed-p hase hplc method. The mean total urinary excretion was 75.4% of the ad ministered dose. The major metabolites present in the urine were conju gates of 2-OHPMP-NO (54.4%) and of 2-OHPMP (18.6%). The excretion of t he unchanged drug, unconjugated 2-OHPMP and 2-OHPMP-NO accounted for 1 .1, 1.1 and 0.2% of the dose respectively.