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.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905.
A J
AJ
Tomlinson
L M
LM
Benson
J W
JW
Gorrod
S
S
Naylor
D000818:Animals; D001711:Biotransformation; D004586:Electrophoresis / Q000379:methods*; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000302:isolation & purification / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000302:isolation & purification / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism; D014867:Water
D006635:Histamine H2 Antagonists; D007093:Imidazoles; D014867:Water; C039796:mifentidine