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

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.

Postmortem Metabolomics of Insulin Intoxications and the Potential Application to Find Hypoglycemia-Related Deaths

“…Postmortem metabolomics has been suggested as a tool in death investigation, with prior publications demonstrating the applicability in discriminating deaths attributable to pneumonia [5] and oxycodone intoxication [6]. These previous studies demonstrated the robustness of combining postmortem metabolomics and multivariate modeling, with validation testing resulting in sensitivity and specificity values between 80-86% and 76-84% [5,6].…”

“…Previously, only a few studies have investigated the associations between metabolome differences and postmortem interval (PMI) [2][3][4]. However, advances have been made recently in expanding the utility of untargeted metabolomics as a potential tool in death investigations, specifically in deaths related to pneumonia [5] and oxycodone intoxication [6]. In these studies, untargeted metabolomics using multivariate statistical modeling could classify specific causes of death, with high sensitivity and specificity, based on the metabolic fingerprint of postmortem blood samples [5,6].…”

“…However, advances have been made recently in expanding the utility of untargeted metabolomics as a potential tool in death investigations, specifically in deaths related to pneumonia [5] and oxycodone intoxication [6]. In these studies, untargeted metabolomics using multivariate statistical modeling could classify specific causes of death, with high sensitivity and specificity, based on the metabolic fingerprint of postmortem blood samples [5,6]. In addition, metabolomics has been used within a forensic context to investigate cause of death using cerebrospinal fluid [7], in a case employing urinary postmortem metabolomics [8], as well as postmortem redistribution Metabolites 2023, 13, 5 2 of 17 mechanisms [9].…”

Metabolomic Studies and Its Importance in the Field of Toxicology: Traditional Review

“…Bu biyokimyasal değişiklikler, oksikodon zehirlenmelerinde potansiyel bir biyobelirteç olarak açilkarnitinlerin kullanılabileceğini göstermiştir. 66 Son yıllarda adli toksikolojide ölüm ile cesedin bulunması arasındaki süre olan postmortem intervali (PMI) de araştırmak için de metabolom analizleri daha sık kullanılmaya başlanmıştır. Bu da adli toksikoloji alanında metabolomik yaklaşımların kullanıldığı diğer bir alandır.…”

Oxycodone in Forensic Toxicology : Analytical Strategies and Interpretation

“…The metabolomics methodology has emerged during the last 20 years and is yet in a relatively early phase of development but has so far proven valuable. Post mortem metabolomics could be a future analytical strategy used in post mortem toxicology (102,106).…”