title: Determination of a cyclooxygenase II inhibitor in human plasma by capillary gas chromatography with mass spectrometric detection.
abstract: Sensitive methods based on capillary gas chromatography (GC) with mass spectrometric (MS) detection in a selected-ion monitoring mode (SIM) for the determination of a cyclooxygenase II (COX-II) inhibitor (3-isopropoxy-4-(4-methanesulfonylphenyl)-5,5'-dimethyl-5H-furan-2-one, I) in human plasma, in two concentration ranges of 0.1-20 and 5-1000 ng/ml, are described. Following liquid-liquid extraction, the residue, after evaporation of the organic phase to dryness, was reconstituted in acetonitrile (20 l) and part of the extract (1 l) was analyzed by GC/MS/SIM. The drug (I) and internal standard (II) were separated on a 25 mx0.2 mm capillary column with HP Ultra 1 (100% dimethylpolysiloxane, 0.33 m) phase and analyzed by MS/SIM monitoring ions at m/z 237 and 282 for I and II, respectively. The standard curve was linear within the lower concentration range of 0.1-20 ng/ml and the lower limit of quantification (LLOQ) in plasma was 0.1 ng/ml. Intraday coefficients of variation (CV, n=5) were 8.9, 4.2, 5.7, 3.1, 1.9, 1.9, and 4.4% at 0.1, 0.2, 0.5, 1.0, 5.0, 10, and 20 ng/ml, respectively. The standard curve was also linear within the higher concentration range of 5-1000 ng/ml and the LLOQ in plasma was 5 ng/ml. Intraday coefficients of variation (CV, n=5) were all below 9% at all concentrations within the standard curve range. The accuracy for I in human plasma was 91-112% and the recovery of I and II was greater than 70% at all concentrations within both standard curve ranges. The details of the assay methodology are presented.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, Merck & Co. Inc., P.O. Box 4, West Point, PA 19486, USA. james_dru@merck.com
authors.forename: J D-Y
authors.initials: JD
authors.lastname: Dru
authors.forename: C M
authors.initials: CM
authors.lastname: Chavez-Eng
authors.forename: M L
authors.initials: ML
authors.lastname: Constanzer
authors.forename: B K
authors.initials: BK
authors.lastname: Matuszewski
mesh_terms: D016861:Cyclooxygenase Inhibitors / Q000097:blood*; D005663:Furans / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C472826:3-isopropoxy-4-(4-methanesulfonylphenyl)-5,5'-dimethyl-5H-furan-2-one; D016861:Cyclooxygenase Inhibitors; D005663:Furans