title: Fully automated liquid-liquid extraction for the determination of a novel insulin sensitizer in human plasma by heated nebulizer and turbo ionspray liquid chromatography-tandem mass spectrometry.
abstract: I, 2-{[5,7-dipropyl-3-(trifluoromethyl)-1,2-benzisoxazol-6-yl]oxy}-2-methyl propionic acid is an alpha peroxisome proliferator-activated receptor (PPAR) agonist with some gamma activity being investigated for potential use in the treatment of Type II diabetes mellitus and dyslipidemia. Two automated liquid-liquid extraction methods were developed and validated for the determination of I in human plasma. Concentrations of I were determined over a wide range of clinical doses. For Method A, plasma was acidified and extracted with ethyl acetate using a fully automated procedure. Analysis was performed by LC-MS/MS with a turbo ionspray source in negative ion mode. For Method B, a larger volume of plasma was extracted and a heated nebulizer source was used on the mass spectrometer. Method A was linear from 0.05 to 50 ng/mL and Method B from 0.2 to 1000 ng/mL. Validation procedures showed that both methods were robust, specific and reproducible.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA. kerry_riffel@merck.com
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Riffel
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Groff
authors.forename: Larissa
authors.initials: L
authors.lastname: Wenning
authors.forename: Hengchang
authors.initials: H
authors.lastname: Song
authors.forename: Man-Wai
authors.initials: MW
authors.lastname: Lo
mesh_terms: D001331:Automation; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D007333:Insulin Resistance; D007555:Isoxazoles / Q000494:pharmacology*; D009330:Nebulizers and Vaporizers; D011422:Propionates / Q000494:pharmacology*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: C503385:2-((5,7-dipropyl-3-(trifluoromethyl)-1,2-benzisoxazol-6-yl)oxy)-2-methyl propionic acid; D007555:Isoxazoles; D011422:Propionates