INVESTIGATION OF THE NEUROLEPTIC DRUG HALOPERIDOL AND ITS METABOLITES USING TANDEM MASS-SPECTROMETRY

The in vitro metabolism of haloperidol, a clinically utilized neuroleptic drug, was investigated using guinea pig derived hepatic microsomal incubates. By employing a combination of reversed phase HPLC and tandem mass spectrometry it was revealed that haloperidol was metabolized to at least eight different compounds, including the proposed dopaminergic toxin 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium species and an intermediate metabolite 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridine.