Post Mortem Analysis of Opioids and Metabolites in Skeletal Tissue

Abstract Every year, thousands of suspicious deaths are accounted for by an overdose of opioids. Occasionally all traditional matrices are unavailable due to decomposition. Skeletal tissue may pose a valid alternative. However, reference data on post-mortem concentrations in bone tissue and bone marrow is sparse. Therefore, a liquid chromatography tandem mass spectrometry method was developed and fully validated for the analysis of 4 opioids and 2 metabolites (tramadol, O-desmethyltramadol, morphine, fentanyl, norfentanyl, codeine) in bone tissue and bone marrow. Sample preparation was performed using solid phase extraction (bone marrow), methanolic extraction (bone) and a protein precipitation (whole blood). All validation parameters were successfully fulfilled. This method was applied to analyze 22 forensic cases involving opioids. All 6 opioids were proven to be detectable and quantifiable in all specimens sampled. When tramadol blood concentrations were correlated with bone concentrations, a linear trend could be detected. The same was seen between tramadol blood and bone marrow concentration. A similar linear trend was seen when correlating codeine blood concentration with bone and bone marrow concentration. Although some variability was detected, the same linear trend was seen for morphine. For fentanyl and norfentanyl, the sample size was too small to draw conclusions, regarding correlation. As far as the authors know this is the first-time fentanyl and norfentanyl are quantified in skeletal tissue. In conclusion, due to the absence of reference data for drugs in skeletal tissue, these findings are a step forward towards a more thorough understanding of drug concentration found in post-mortem skeletal tissue.

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Method Validation of Seven Synthetic Cathinones by LC–MS-MS Analysis and the Prevalence of N-Ethylpentylone in Postmortem Casework

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa194 ◽

2020 ◽

Author(s):

Alexander D Giachetti ◽

Joseph H Kahl ◽

M Elizabeth Zaney ◽

George W Hime ◽

Diane M Boland

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Solid Phase ◽

Synthetic Cathinones ◽

Medical Examiner ◽

Tandem Mass ◽

Blood Concentrations ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

Abstract N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016 to 2018. There is limited information regarding the toxicity of NEP; however, the few published reports suggest that NEP can cause serious toxic effects and sudden death. The purpose of this publication is to describe a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method for seven synthetic cathinones (methylone, ethylone, butylone, dibutylone, alpha-Pyrrolidinopentiophenone (α-PVP), pentylone and NEP) and to present a detailed summary regarding the presence of NEP in postmortem casework at the Miami-Dade Medical Examiner Department. Postmortem iliac blood, serum, liver and brain specimens were prepared by solid-phase extraction with analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. Analyte linearity was established from 0.01 to 0.5 mg/L on a six-point calibration curve. A total of 101 NEP quantitations were performed using this method. Concentrations in postmortem case samples ranged from 0.01 to 2.7 mg/L. Iliac blood concentrations averaged 0.312 mg/L with a median of 0.137 mg/L (n = 72) across all causes and manners of death. Approximately half of the cases were homicides in which the decedent was the victim of gunshot wounds or stabbing. Two of the three highest concentration cases of NEP (2.7 and 1.7 mg/L) involved 38-year-old white males who were tasered by police prior to death. The psychostimulant effect of NEP may result in an excited delirium and/or hallucinogenic state. The concentration of NEP detected in accidental intoxication and polydrug cases overlapped with those attributed to other causes, including homicides and police-involved deaths.

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