Identification of rat faecal, urinary and biliary metabolites of thionorphine, a novel mixed agonist-antagonist analgesic, using liquid chromatography/electrospray ionization tandem mass spectrometry

The biotransformation of thionorphine (N-cyclopropylmethyl-7alpha-[(s)-1-hydroxy-1-methyl-3-(2thiophene) -propyl]-6,14-endo-ethano tetrahydrooripavine), a new analgesic, was investigated in rats. The results of metabolite analysis by liquid chromatography/electrospray ionization tandem mass spectrometry with positive ion mode, in which a mobile phase of 10 mM ammonium acetate (pH 3.0)/acetonitrile (25/75) was used, suggested that thionorphine is biotransformed to two potentially active metabolites, the N-dealkylated thionorphine (M-I) and the oxidized thionorphine (M-II), and subsequently form conjugates with glucuronic acid of both thionorphine and the metabolites. Copyright (C) 2004 John Wiley Sons, Ltd.