title: Quantitative determination of MK-0767, a dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist, in human plasma by liquid chromatography-tandem mass spectrometry.
abstract: 5-[2,4-Dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[(4-trifluoromethyl)-phenyl]methyl]benzamide (I, MK-0767 or KRP-297, Fig. 1), is a dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist. A LC-MS/MS method for the determination of I in human plasma has been successfully developed, validated and applied to clinical programs. The analyte and internal standard (II) are extracted from 0.05 mL plasma via solid phase extraction (SPE). HPLC is used for the separation of I and II from possible co-extracted endogenous and other compounds. Detection is by MS/MS in multiple reaction monitoring (MRM) mode using a TurboIonSpray probe. The whole sample preparation is automated by using a Packard Multiprobe liquid handling system. The linear range is 4-2000 ng/mL in plasma. Recoveries were 71.1% and 69.4% for I and II, respectively. The method exhibited good linearity, reproducibility and sensitivity, selectivity and robustness when used for the analysis of clinical samples.
authors.affiliation: Merck Research Laboratories, Department of Drug Metabolism, WP75A-303, West Point, PA 19486, USA. henry_song@merck.com
authors.forename: Hengchang
authors.initials: H
authors.lastname: Song
authors.forename: Kerri
authors.initials: K
authors.lastname: Yan
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Man-Wai
authors.initials: MW
authors.lastname: Lo
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005615:Freezing; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D013048:Specimen Handling; D013844:Thiazoles / Q000097:blood*
chemical_list: D007202:Indicators and Reagents; C487303:MK0767; D047493:PPAR alpha; D047495:PPAR gamma; D013844:Thiazoles