A1 Refereed original research article in a scientific journal

Determination of total and unbound sufentanil in human plasma by ultrafiltration and LC-MS/MS: Application to clinical pharmacokinetic study




AuthorsSaari TI, Fechner J, Ihmsen H, Schuttler J, Jeleazcov C

PublisherELSEVIER SCIENCE BV

Publication year2012

JournalJournal of Pharmaceutical and Biomedical Analysis

Journal name in sourceJOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Journal acronymJ PHARMACEUT BIOMED

Volume66

First page 306

Last page313

Number of pages8

ISSN0731-7085

DOIhttps://doi.org/10.1016/j.jpba.2012.03.050


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. (C) 2012 Elsevier B.V. All rights reserved.



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