title: Quantitative measurement of propofol and in main glucuroconjugate metabolites in human plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry.
abstract: A high-performance liquid chromatographic method coupled with tandem mass spectrometry detection has been developed for the determination of propofol and its main glucuroconjugate metabolites (propofol-glucuronide (PG), 1-quinol-glucuronide (1-QG) and 4-quinol-glucuronide (4-QG) in human plasma. All compounds were extracted with a single solid phase extraction procedure using Max Oasis cartridges. Propofol and thymol (internal standard) were analyzed using a C8 reversed-phase column with a mobile phase consisting of methanol-water (75:25, v/v) containing 0.025% NH(4)OH. Chromatography of glucuroconjugate metabolites and phenyl-beta-d-glucuronide (internal standard) was performed using a hydrophilic interaction liquid chromatography (HILIC) and a mixture of acetonitrile/water/ammonium acetate buffer (100 mM, pH 5, 87/1/12, v/v/v). Both chromatographic separations were achieved in isocratic mode allowing a rapid analysis without re-equilibration of the phase. The method is specific and sensitive with a range of 10-1500 ng mL(-1) for propofol and 1-QG, 20-3000 ng mL(-1) for PG and 25-3750 ng mL(-1) for 4-QG. The regression curves were linear for all compounds. The method is accurate and precise with intra-assay and inter-assay precision <8% and bias < or =6% for all compounds. This assay has allowed the successful measurement of propofol and its main glucuroconjugate metabolites in human plasma from 24 patients undergoing anaesthesia for elective partial hepatectomy surgery.
authors.affiliation: Hospices Civils de Lyon, Fédération de Biochimie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: F
authors.initials: F
authors.lastname: Lhuillier
authors.forename: Y
authors.initials: Y
authors.lastname: Mouloua
authors.forename: B
authors.initials: B
authors.lastname: Vignal
authors.forename: P
authors.initials: P
authors.lastname: Favetta
authors.forename: J
authors.initials: J
authors.lastname: Guitton
mesh_terms: D018686:Anesthetics, Intravenous / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015742:Propofol / Q000097:blood*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol