Investigation of the metabolism of the neuroleptic drug haloperidol by capillary electrophoresis.

Free solution capillary electrophoresis (FSCE) conditions were previously reported to be of limited use for the separation of pharmaceuticals, since many of these compounds are neutral. We show that by consideration of compound hydrophobicity and ionisable functional groups, FSCE conditions can be developed to effect the separation of a drug and its phase I metabolites. This is brought about by adding a suitable organic modifier to aid solubility, and modifying pH to effect a change in the mass to charge ratio of the metabolites present. Furthermore, we show that in this drug metabolism study, FSCE presents an advantage over both reversed-phase HPLC and micellar electrokinetic chromatography. We also demonstrate the use of FSCE for investigation of the phase I metabolites produced by the in vitro incubation of haloperidol (a neuroleptic agent) with both mouse and guinea pig hepatic microsomes and show that such an approach can be used to detect both qualitative and quantitative differences in species metabolism.