Analytical considerations for postmortem metabolomics using GC-high-resolution MS
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RESEARCH PAPER
Analytical considerations for postmortem metabolomics using GC-high-resolution MS Lana Brockbals 1 & Thomas Kraemer 1 & Andrea E. Steuer 1 Received: 1 September 2019 / Revised: 18 October 2019 / Accepted: 31 October 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract Metabolomics studies that aim to qualitatively and quantitatively characterize the entirety of small endogenous biomolecules in an organism are widely conducted in the clinical setting. They also become more and more popular in the field of forensics (toxicology), e.g., to assist in postmortem investigations by objective postmortem interval estimation. However, other issues in postmortem toxicology, such as the phenomenon of (time-dependent) postmortem redistribution, have not yet been tackled by metabolomics studies. Hence, the aim of the current study was to develop an (un)targeted gas chromatography-high-resolution mass spectrometry–based method for endogenous metabolites as a tool for large-scale (un)targeted human postmortem metabolomics investigations (e.g., to objectively assess PMR) with thorough analytical evaluation of this method to ensure fitness-topurpose in terms of reliability and robustness. This was achieved by using a targeted metabolite subset (n = 56) and a targeted processing workflow. Evaluation experiments have shown that using an artificial matrix (revised simulated body fluid (rSBF) + 5% bovine serum albumin (BSA)) for calibration purposes, all parameters lay within the scope of the method (sensitivity, selectivity, calibration model, accuracy, precision, processed sample stability, and extraction efficiency). When applying this method to large-scale studies, samples should be run in randomized order if analysis time is expected to exceed 18–24 h and potential biomarkers that are found with this method should be verified by a specialized, targeted method (e.g., by using standard addition in authentic matrix for quantification purposes). Overall, the current method can be successfully used for conduction of time-dependent postmortem metabolomics investigations. Keywords Postmortem metabolomics . GC-MS . Forensic toxicology . Method evaluation . High resolution
Introduction The term metabolomics (also known as metabolic profiling or metabonomics) refers to the study of the metabolism and metabolites in an organism, aiming to qualitatively and quantitatively characterize and identify the entirety of small endogenous biomolecules (< 1000 Da) and statistically determine changes between two or more conditions. It has proven to be an effective tool e.g. in biomarker research, metabolic pathway confirmation, drug discovery, and studies of diseases. Published in the topical collection featuring Female Role Models in Analytical Chemistry. * Andrea E. Steuer [email protected] 1
Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich, Switzerland
Particularly in the clinical setting, a number of
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