Postmortem Metabolomics Reveal Acylcarnitines as Potential Biomarkers for Fatal Oxycodone-Related Intoxication.

Albert Elmsjö,Robert Kronstrand,Carl Söderberg,Gerd Jakobsson,Henrik Green

doi:10.3390/metabo12020109

Albert Elmsjö, Robert Kronstrand + Show 3 more

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https://doi.org/10.3390/metabo12020109

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Abstract

Postmortem metabolomics has recently been suggested as a potential tool for discovering new biological markers able to assist in death investigations. Interpretation of oxycodone concentrations in postmortem cases is complicated, as oxycodone tolerance leads to overlapping concentrations for oxycodone intoxications versus non-intoxications. The primary aim of this study was to use postmortem metabolomics to identify potential endogenous biomarkers that discriminate between oxycodone-related intoxications and non-intoxications. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry data from 934 postmortem femoral blood samples, including oxycodone intoxications and controls positive and negative for oxycodone, were used in this study. Data were processed and evaluated with XCMS and SIMCA. A clear trend in group separation was observed between intoxications and controls, with a model sensitivity and specificity of 80% and 76%. Approximately halved levels of short-, medium-, and long-chain acylcarnitines were observed for oxycodone intoxications in comparison with controls (p < 0.001). These biochemical changes seem to relate to the toxicological effects of oxycodone and potentially acylcarnitines constituting a biologically relevant biomarker for opioid poisonings. More studies are needed in order to elucidate the potential of acylcarnitines as biomarker for oxycodone toxicity and their relation to CNS-depressant effects.

Highlights

Metabolomics strives at quantifying as many low weight molecules as possible within a well determined biological sample, i.e., the metabolome [1]
The number of metabolomics applications used for death investigations are limited, and most efforts have focused on using metabolomics for predicting time since death [3]
We found a significant decrease in femoral blood for 25 acylcarnitines in intoxication cases in comparison to control cases

Summary

Introduction

Metabolomics strives at quantifying as many low weight molecules as possible within a well determined biological sample, i.e., the metabolome [1]. Metabolomics has proven suitable both for biomarker discovery and for generating new biological hypotheses, and since its introduction has been applied within several of different scientific fields [2]. We recently demonstrated on autopsy cases with pneumonia that postmortem metabolomics could potentially aid in determining the cause of death [4]. Postmortem metabolomics offers a new and unique possibility within the field of forensic toxicology as the postmortem metabolome probably reflects the events leading up to death, the events after death, and potentially the cause of death. Overconsumption of opioids can potentially produce life-threatening respiratory depression through their action on μ-opioid receptors.

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