TY - JOUR T1 - Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1714 LP - 1722 DO - 10.1124/dmd.110.033795 VL - 38 IS - 10 AU - Yi-Chun Lai AU - Tzong-Fu Kuo AU - Chien-Kuang Chen AU - Han-Ju Tsai AU - Shoei-Sheng Lee Y1 - 2010/10/01 UR - http://dmd.aspetjournals.org/content/38/10/1714.abstract N2 - The metabolic profile of dicentrine, a selective α1-adrenoceptor antagonist with potent antiarrhythmic and antihypertensive activities, in miniature pig urine via oral administration was investigated for the first time. The urine, collected after a single oral administration of dicentrine, was pretreated using solvent extraction and column chromatographic methods to identify the metabolites containing fractions. Twenty-four metabolites (MI-1–9 and MII-1-15), of which 21 compounds are new, were identified by mass spectrometry and high-performance liquid chromatography-diode array detector solid-phase extraction-NMR techniques. Of these, 14 metabolites (MI-5, MII-1 and 2, and MII-5-15) were further isolated for structure confirmation. The phase I metabolic transformations of dicentrine were found to be N-demethylation, N-oxidation, O-demethylation (9,10-OMe), O,O-demethylenation (1-OCH2O-2), and hydroxylation at the benzylic (C-4) and the aromatic (C-3) positions, whereas those for the phase II were O-glucuronidation and O-glucosylation of the phenolic group of the phase I metabolites. ER -