Fast and easy extraction of antidepressants from whole blood using ionic liquids as extraction solvent.

Journal: Talanta
Published Date:

Abstract

This study aims to prove that ionic liquids (ILs) can be used as extraction solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the quantification of a large group of antidepressants in whole blood samples. The sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and 60µL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole blood. Subsequently, a 5-min rotary mixing step was performed followed by centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and 10µL was injected into the LC-MS/MS. The following analytes were included in the full-quantitative method: agomelatine, amitriptyline, bupropion, clomipramine, dosulepin, doxepin, duloxetine, escitalopram, fluoxetine, imipramine, maprotiline, mianserin, mirtazapine, nortriptyline, paroxetine, reboxetine, trazodone and venlafaxine. Selectivity was checked for 10 different whole blood matrices. Additionally, possible interferences of deuterated standards or other antidepressants were evaluated. Overall, no interferences were found. For each analyte a matrix-matched calibration curve was constructed (7 levels, n = 6), covering therapeutic and low toxic concentrations. Accuracy and precision were evaluated over eight days, at three concentration levels (n = 2). Bias, repeatability and intermediate precision results met with the proposed validation criteria, except for fluvoxamine, which was therefore only included in the semi-quantitative method. LOQs were set at the lowest calibrator concentration and LOD values were - for most analytes - within a range of 1-2ng/mL. Recoveries (RE) and matrix effects (ME) were evaluated for five types of donor whole blood, at two concentration levels. RE values were within a range of 53.11-132.98%. ME values were within a range of 61.92-123.24%. In conclusion, this study proves the applicability of ILs as extraction solvents for a large group of antidepressants in complex whole blood matrices.

Authors

  • Marieke De Boeck
    Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), Campus Gasthuisberg, O&N II, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium.
  • Lisa Dubrulle
    Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), Campus Gasthuisberg, O&N II, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium.
  • Wim Dehaen
    Molecular Design and Synthesis, Department of Chemistry, University of Leuven (KU Leuven), Campus Arenberg, P.O. Box 2404, Celestijnenlaan 200 F, 3001 Leuven, Belgium.
  • Jan Tytgat
    Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), Campus Gasthuisberg, O&N II, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium.
  • Eva Cuypers
    Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), Campus Gasthuisberg, O&N II, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium. Electronic address: eva.cuypers@kuleuven.be.