Metabolomics of post-mortem blood: identifying potential markers of post-mortem interval

Abstract

Death results in changes in some metabolites in body tissues due to lack of circulating oxygen, altered enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites and macromolecules. Metabolic changes may provide chemical markers to better determine the time since death (post-mortem interval), something that is challenging to establish with current observation-based methodologies. The aim of this research was to carry out a metabolic analysis of blood plasma postmortem, in order to gain a more complete understanding of the biochemical changes that occur following death. Gas chromatography was used to conduct a survey of post-mortem rat blood. Sixty six metabolites were detected post-mortem. Twenty six of these [18 amino acids, glutathione (GSH), 4-Amino-n-butyric acid (GABA), glyoxylate, oxalate, hydroxyproline, creatinine, a-ketoglutarate and succinate] had increased concentrations post-mortem. The remaining 40 metabolites had concentrations that were not dependant on time. This study demonstrates the range of metabolic changes that occur post-mortem as well as identifying potential markers for estimating post-mortem interval.

Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus

“…As a consequence, the lack of ATP related to the post-mortem hypoxia state can compromise the glutathione system. Various papers state that brain glutathione content drops rapidly after death, reflecting the fact that its metabolism is influenced by post-mortem interval (Donaldson and Lamont 2015 ; Perry et al 1981 ; Harish et al 2011 ; Epstein et al 2013 ). According to the explanation above, increased glycine and pyroglutamic acid levels in the hippocampus tissues are consistent with GSH hydrolysis.…”

Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

“…21 Recently, first data have been published on changes in the human metabolome caused by 3,4-methylenedioxymethamphetamine (MDMA). 24 In postmortem investigations, metabolomics could also be used for the estimation of the postmortem interval (PMI) with, for example, amino acids and creatinine being elevated postmortem 25,26 or with sterol sulfates and very-long-chain fatty acids declining during the postmortem period. 17,18 Further, there are increasing analytical problems in the detection of new psychoactive substances (NPS), which are flooding the drug market worldwide.…”

“…Steuer et al also showed that metabolomics can further be applied to detect urine adulterations, a typical problem in forensics. 24 In postmortem investigations, metabolomics could also be used for the estimation of the postmortem interval (PMI) with, for example, amino acids and creatinine being elevated postmortem 25,26 or with sterol sulfates and very-long-chain fatty acids declining during the postmortem period. 27 Forensic analysis and/or interpretation typically require a high degree of accuracy and precision to justify a court decision.…”

“…32 Due to uncertainty of analytes of interest, a combination of a targeted and untargeted method would be ideal to be able to quantify at least some important metabolites and have some validity of the method while maintaining the ability to screen and detect numerous unknown metabolites and features within the same method as, for In the information-dependent acquisition mode (IDA), MS/MS spectra are produced with minimal interferences as only ions within the selected narrow m/z window (typically 1-3 Da wide) are transferred to the collision cell to produce product ions. 34 Sequential window acquisition of all theoretical fragment-ion spectra (SWATH) has medium sized m/z windows (usually [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and is stepped continuously across the whole mass range of interest. SWATH obtains MS/MS data by fragmenting at a much narrower precursor ion window and retains the ability of product ion spectra recording of all precursor ions within a large mass range.…”

UV–Vis and ATR–FTIR spectroscopic investigations of postmortem interval based on the changes in rabbit plasma

“…Contrary to the postmortem redistribution that decreases with the decrease in the concentration gradient, the decomposition effects increase gradually in the early postmortem period till at some time point, the previously hidden effect of decomposition begins to appear. According to previous researches [ 22 , 61 – 63 ], the process of decomposition may also degrade the components in blood, including metabolites, proteins, saccharides, and nucleic acids. Previous studies also proved that the decomposition process had a significant impact on the FTIR spectra of postmortem substantial organs [ 24 , 25 , 27 ].…”