title: Determination of total and unbound sufentanil in human plasma by ultrafiltration and LC-MS/MS: application to clinical pharmacokinetic study.
abstract: A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of sufentanil total and unbound drug concentrations. Unbound drug was separated by an ultrafiltration step before sample preparation. Both the ultrafiltrate and plasma samples were extracted with solid-phase extraction and substituted with deuterated sufentanil used as an internal standard. Separation was performed by gradient elution using UPLC-like system and analysed by MS/MS consisting of an electrospray ionization source. Calibration curves showed linearity in the concentration range of 5-2500 pg/ml for analysis of both total and unbound concentrations of sufentanil. The lower limit of quantification was 5 pg/ml for both total and unbound sufentanil plasma drug concentrations. Intra- and interassay precision and accuracy did not exceed 15%. Method was applied to pharmacokinetic study in patients undergoing coronary artery bypass grafting.
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. teijo.saari@gmail.com
authors.forename: Teijo I
authors.initials: TI
authors.lastname: Saari
authors.forename: Jörg
authors.initials: J
authors.lastname: Fechner
authors.forename: Harald
authors.initials: H
authors.lastname: Ihmsen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schüttler
authors.forename: Christian
authors.initials: C
authors.lastname: Jeleazcov
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D001026:Coronary Artery Bypass / Q000379:methods; D006801:Humans; D057230:Limit of Detection; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D017409:Sufentanil / Q000008:administration & dosage / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014462:Ultrafiltration / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D017409:Sufentanil