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WIREs Forensic Sci

Antemortem and postmortem influences on drug concentrations and metabolite patterns in postmortem specimens

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When interpreting postmortem analytical data, toxicologists must be aware that postmortem concentrations of xenobiotics and/or their metabolites may be influenced by many factors. Some of these influences occur antemortem like the general pharmacokinetic properties of the xenobiotic or individual pharmacokinetics in the particular subject. They determine the concentrations at the time of death and may be relevant for the determination of the manner rather than the cause of death. Other influences occurring postmortem include continuing drug metabolism, chemical, and/or microbial degradation as well as potential postmortem formation of some toxicologically relevant compounds. Such postmortem effects may tremendously change the concentrations of xenobiotics and/or their metabolites at the time of death. If not adequately considered, this may lead to false conclusions regarding the involvement of the respective xenobiotic in the cause of death. The present article will provide an overview on antemortem and postmortem effects giving examples from the literature. It will also discuss if and how such effects may be identified based on postmortem specimens and, in case of the postmortem effects, how they may be reduced by proper storage and addition of stabilizers like fluoride salts. This article is categorized under: Toxicology > Post‐Mortem Toxicology Toxicology > Analytical Toxicology Toxicology > Drug Stability
Plasma concentations of heroin (upper panels), 6‐monoacetyl morphine (6‐MAM, middle panels), and morphine (lower panels) after intravenous (left panels) and intranasal (right panels) administration as a function of time and dose. Data points represent the mean concentration after administration of the given doses in mg or placebo (Pbo) to six subjects each. Error bars represent ±1SEM. (Reprinted with permission from Comer, Collins, MacArthur, and Fischman (). Copyright 1999 Springer Nature)
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HPLC–DAD stability results of risperidone spiked into equine blood and case blood showing production of the suspected risperidone scission product. (Reprinted with permission from Taylor and Elliott (). Copyright 2013 Wiley)
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Stability of cathinone (filled diamonds), methcathinone (filled squares), ethcathinone (filled triangles), mephedrone (open squares), amfepramone (crosses), flephedrone (filled circles), methedrone (open triangles), methylone (open diamonds), and butylone (open circles) in final extracts of live blood fortified with 100 μg/L of each substance and then stored at 20 ± 2°C for 7 days as function of the pH of the final sample extracts. (Reprinted with permission from Sorensen (). Copyright 2011 Elsevier)
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Median (a) tramadol/O‐demethyltramadol (MR1) and (b) tramadol/nortramadol (MR2) concentration ratios with 95% confidence intervals in postmortem blood of four groups CYP2D6 genotypes. Group 0, no functional alleles; group 1, one functional allele; group 2, two functional alleles; group 3, three or more functional alleles. (Reprinted with permission from Levo et al. (). Copyright 2003 Elsevier)
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Toxicology > Analytical Toxicology
Toxicology > Drug Stability
Toxicology > Post-Mortem Toxicology

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