title: Determination of total and unbound propofol in patients during intensive care sedation by ultrafiltration and LC-MS/MS.
abstract: For the quantification of propofol total and unbound drug concentrations a sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. To separate unbound propofol an ultrafiltration step before sample preparation was performed. Both the ultrafiltrate and plasma samples were extracted with solid-phase extraction and substituted with deuterated propofol as an internal standard. Separation was performed by gradient elution using UPLC-like system and analyzed by MS/MS consisting of an electrospray ionization source. To detect low and high concentration levels of propofol two calibration curves were identified and showed linearity within the range of 1-50ng/ml and 50-20000ng/ml. The lower limit of quantification was 1ng/ml. Intra- and interassay precision and accuracy did not exceed ±15%. The method was applied to a clinical study during intensive care treatment of patients after coronary artery bypass grafting.
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany. Electronic address: andreas.eisenried@kfa.imed.uni-erlangen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Eisenried
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wehrfritz
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Ihmsen
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schüttler
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstraße 12, 91054 Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jeleazcov
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D001026:Coronary Artery Bypass / Q000379:methods; D003422:Critical Care; D006801:Humans; D006993:Hypnotics and Sedatives / Q000032:analysis / Q000493:pharmacokinetics*; D057230:Limit of Detection; D015742:Propofol / Q000032:analysis / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014462:Ultrafiltration / Q000379:methods
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol
keywords: Liquid chromatography; Mass spectrometry; Pharmacokinetic; Propofol; Target-controlled infusion (TCI); Unbound