Determination of total and unbound propofol in patients during intensive care sedation by ultrafiltration and LC-MS/MS

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 1-50 ng/ml and 50-20000 ng/ml. The lower limit of quantification was 1 ng/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. (C) 2016 Elsevier B.V. All rights reserved.