Characterization of olanzapine (LY170053) in human liver slices by liquid chromatography tandem mass spectrometry

Olanzapine metabolism was investigated using incubation of olanzapine with human liver slices. The intent of the investigation was to identify olanzap ine metabolites and determine if the human liver slice incubations could po tentially produce quantities of the olanzapine glucuronides for future stud ies. Along with known Phase 1 olanzapine metabolites, N-desmethyl-, 2-hydro xymethyl-, and 4'-N-oxide-, a new hydroxylated species was detected. Detect ion of Phase 2 metabolites included known N-10-glucuronides, a quaternary g lucuronide and a novel glucuronide conjugate. This investigation showed the feasibility of using human liver slices to produce sufficient quantities o f olanzapine glucuronides for further studies. (C) 1998 John Whey & Sons, L td.