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.
Tomlinson
A J
AJ
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905.
Benson
L M
LM
Gorrod
J W
JW
Naylor
S
S
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