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  • Title: Urinary metabolic profile in rat of 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone: a potential radioligand for functional diagnosis of adrenal pathology.
    Author: Damani LA, Mitterhauser M, Lin G, Ho YP, Zolle I.
    Journal: Xenobiotica; 1996 Feb; 26(2):211-19. PubMed ID: 8868004.
    Abstract:
    1. The metabolism of 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone (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 were also isolated by preparative tlc, and analyzed by direct probe mass spectrometry. In the case of conjugated metabolites, the urine samples were deconjugated by enzyme hydrolysis prior to extraction. The structures of metabolites were confirmed by comparison of their chromatographic behaviours, UV spectra, and mass spectra with those of authentic standards. 3. The metabolites identified in the 0-24-h urine samples were 2-hydroxyphenyl-metyrapone (2-OHPMP) and 2-hydroyphenylmetyrapone N-oxide (2-OHPMP-NO), which were present predominantly as their glucuronide and/or sulphate conjugates. 4. 2-MPMP and four of its metabolites present in the 0-24-h urine samples were quantified by a reversed-phase hplc method. The mean total urinary excretion was 75.4% of the administered dose. The major metabolites present in the urine were conjugates of 2-OHPMP-NO (54.4%) and of 2-OHPMP (18.6%). The excretion of the unchanged drug, unconjugated 2-OHPMP and 2-OHPMP-NO accounted for 1.1, 1.1 and 0.2% of the dose respectively.
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