title: Rapid determination of soluble epoxide hydrolase inhibitors in rat hepatic microsomes by high-performance liquid chromatography with electrospray tandem mass spectrometry.
abstract: A rapid and reliable electrospray tandem mass spectrometric method for soluble epoxide hydrolase (sEH) inhibitors in rat hepatic microsomes is described. Four synthesized sEH inhibitors were extracted from rat hepatic microsomes with ethyl acetate and were determined by HPLC using positive ion electrospray tandem mass spectrometry within 7 min. The relationship between signal intensity and concentration of sEH inhibitors was linear over the concentration range of 2.0 to 500 ng/mL per 5-microL injection with the use of a noncoeluting internal standard with a similar chemical structure. The intraassay precision was less than 12.4% relative standard deviation and accuracy ranged from -7.0 to 11.3% deviation from the theoretical values with five duplicate assays. The recovery of sEH inhibitors from rat hepatic microsomes, fortified at levels of 50, 100, and 250 ng/mL, averaged 74.2-107.7% with a RSD of 2.1-7.6%. This method was successfully applied to the quantification of residual sEH inhibitors in rat hepatic microsomes without interference.
authors.affiliation: Department of Entomology and Cancer Research Center, University of California, Davis, CA 95616, USA.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: B D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014508:Urea / Q000031:analogs & derivatives* / Q000032:analysis* / Q000494:pharmacology
chemical_list: C450240:1-adamantan-1-yl-3-cyclohexyl-urea; C450241:1-cyclohexyl-3-decyl-urea; C450146:1-cyclohexyl-3-dodecylurea; C450243:1-cyclohexyl-3-tetradecyl-urea; D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases; D000218:Adamantane; C000948:1,3-dicyclohexylurea