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Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional 13C isotope monitoring

Staeheli, Sandra ; Poetzsch, Michael ; Kraemer, Thomas ; Steuer, Andrea

In: Analytical and Bioanalytical Chemistry, 2015, vol. 407, no. 29, p. 8681-8712

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    Titel
    • Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional 13C isotope monitoring
    Autor
    • Staeheli, Sandra. Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057, Zurich, Switzerland
    • Poetzsch, Michael. Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057, Zurich, Switzerland
    • Kraemer, Thomas. Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057, Zurich, Switzerland
    • Steuer, Andrea. Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057, Zurich, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Analytical and Bioanalytical Chemistry, 2015, vol. 407, no. 29, p. 8681-8712. Springer Berlin Heidelberg
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:331589
    Summary
    Postmortem redistribution (PMR) is one of numerous problems in postmortem toxicology making correct interpretation of measured drug concentrations difficult or even impossible. Time-dependent PMR in peripheral blood and especially in tissue samples is still under-explored. For further investigation, an easy applicable method for the simultaneous quantitation of over 80 forensically relevant compounds in 11 different postmortem matrices should be developed and validated overcoming the challenges of high inter-matrix and intra-matrix concentration variances. Biopsy samples (20mg) or body fluids (20μL) were spiked with an analyte mix and deuterated internal standards, extracted by liquid-liquid extraction, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). For highest applicability, an easy solvent calibration was used. Furthermore, time-consuming dilution of high concentration samples showing detector saturation was circumvented by two overlapping calibration curves using 12C isotope monitoring for low concentrations and 13C isotopes for high concentration, respectively. The method was validated according to international guidelines with modifications. Matrix effects and extraction efficiency were strongly matrix and analyte dependent. In general, brain and adipose tissue produced the highest matrix effects, whereas cerebrospinal fluid showed the least matrix effects. Accuracy and precision results were rather matrix independent with some exceptions. Despite using an external solvent calibration, the accuracy requirements were fulfilled for 66 to 81% of the 83 analytes. Depending on the matrix, 75-93% of the analytes showed intra-day precisions at <20%. 12C and 13C calibrations gave comparable results and proved to be a useful tool in expanding the dynamic range.