In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver preparations using liquid chromatography/electrospray mass spectrometry

The in vitro metabolism of a new erectogenic, DA-8159, has been studied by LC with UV detection and on-line LC-electrospray mass spectrometry using rat hepatic microsomal incubation and rat liver perfusion. Both rat liver microsomal incubation of DA-8159 in the presence of NADPH and single-pass liver perfusion of DA-8159 resulted in the formation of three metabolites (M1-3). M1 was tentatively identified as hydroxy-DA-8159. M2 and M3 were identified as N-demethyl-DA-8159 and 5-(2-propyloxy-5-aminosulphonylphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one (DA-8164), respectively, on the basis of LC-MS/MS analysis with authentic standards. Rat CYP2D1 was a major isozyme for the formation of hydroxy-DA-8159 and N-demethyl-DA-8159. CYP2C12 and CYP1A1 catalysed the oxidation of DA-8159 to DA-8164.