Investigation of the in vitro metabolism of the H2-antagonist mifentidine by on-line capillary electrophoresis-mass spectrometry using non-aqueous separation conditions.

The in vitro metabolism of mifentidine, a prototype second-generation histamine H2-antagonist, is investigated using on-line capillary electrophoresis-mass spectrometry (CE-MS) by analysis of hepatic microsomal incubates. Consideration of the hydrophobicity of this drug and putative metabolites led to the development of a non-aqueous CE separation medium consisting of 5 mM NH4OAc in methanol containing 100 mM acetic acid. Benefits of non-aqueous media in CE-MS studies of small hydrophobic molecules are discussed. In addition, we elucidate both chemical transformations and the in vitro metabolism of mifentidine using guinea pig hepatic microsomes.