Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat

RGH-1756, 1-(2-methoxy-phenyl)-4-{4-[4-(6-imidazol[2,1-b] thiazolyl)-phenox y]-butyl-4-C-14}-piperazine dimethane is a novel atypical antipsychotic dru g candidate of Gedeon Richter Ltd. The metabolic pathways of the compound h ave been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with C-14-RGH-1756. The metabolites for med in vitro by rat liver microsomes have also been analysed. Good separati on of the compounds has been achieved by gradient HPLC method on Zorbax/Bon us RP-C18 column. Radiometry and mass spectrometry have been applied to det ect and characterise the metabolites. The metabolite formed by oxidative cl eavage of the chain at the carbon atom adjacent to the piperazine nitrogen has been identified as the major plasma metabolite. Glucuronide conjugate o f hydroxy-RGH-1756 has been found as one of the main metabolites excreted i n the bile where the unchanged compound has not been detected. (C) 2001 Els evier Science B.V. All rights reserved.