Journal Article

Distribution of synthetic opioids in postmortem blood, vitreous humor and brain

Cooper, Gail, Chesser, Rachel, Concheiro, Marta, Pardi, Justine

2019

Overview

•Methods were validated for detection of 15 synthetic opioids in postmortem samples.•Six synthetic opioids were detected in authentic cases (n=58).•Concentrations were within 0.1–100ng/mL or ng/g.•Acetylfentanyl and U-47700 concentrations exceeded 100ng/mL or ng/g.•Highest concentrations were observed in brain, followed by blood and vitreous humor. In the US, the use of synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses and interpretation of synthetic opioids has become extremely important. However, due to the novelty of these compounds, the available data are limited and provides challenges to toxicologists. The objectives of this study were (1) to develop and validate analytical methods for the determination of synthetic opioids in vitreous humor and brain, and (2) to investigate the postmortem distribution of new synthetic opioids in blood, vitreous humor, and brain tissue. Vitreous humor (0.5mL) and brain tissue (5g) homogenized in water (diluted 1:3, w/w) were extracted by mixed mode cation exchange-reversed phase solid phase extraction. Extracts were analyzed by liquid chromatography tandem mass spectrometry (LC–MSMS). The chromatographic separation was performed by reversed-phase with 0.1% formic acid in water and in acetonitrile as mobile phases in gradient mode, with a total run time of 21min. Data were acquired with ESI+ in dynamic multiple reaction mode (dMRM), monitoring 2 transitions per compound. The methods were succesfully validated following SWGTOX guidelines, with limits of quantification of 0.1ng/mL in vitreous humor and 0.1ng/g in brain. Fifty-eight authentic case samples from the New York City Office of the Chief Medical Examiner (NYC-OCME) were analyzed to assess the distribution and detectability of synthetic opioids in these postmortem samples. Of the fifteen synthetic opioids included in the method, six synthetic opioids and metabolites (4-ANPP, acetylfentanyl, fentanyl, furanylfentanyl, norfentanyl, U-47700) were detected in the authentic cases. Concentrations for most analytes were within the 0.1 to 100ng/mL or ng/g calibration range across all three matrices, with only concentrations from acetylfentanyl and U-47700 exceeding 100ng/mL or ng/g. The highest concentrations were observed in brain (except norfentanyl), followed by blood and vitreous humor. Most analytes were detected in all three matrices in a given case. This was followed by detection of an analyte in combinations of brain and another matrix or brain only. Through the case analyses, vitreous humor and brain demonstrated to be viable alternatives to blood when performing postmortem analyses of synthetic opioids. Brain exhibited a higher detectability for most analytes when compared to blood and vitreous humor.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Acetonitrile / Analgesics, Opioid - analysis / Analgesics, Opioid - pharmacokinetics / Analytical methods / Autopsy / Bias / Blood / Brain / Brain Chemistry / Calibration / Cation exchange / Cation exchanging / cations / chemical species / Chromatography, Liquid / Data acquisition / Drugs / Fentanyl / Forensic sciences / Forensic Toxicology / Formic acid / guidelines / Humans / Liquid chromatography / Mass spectrometry / Mass spectroscopy / Metabolites / monitoring / mortality / Narcotics / New York / Opioids / Overdose / Postmortem / Psychotropic Drugs - analysis / Psychotropic Drugs - pharmacokinetics / Solid Phase Extraction / Solid phases / Synthetic Drugs - analysis / Synthetic Drugs - pharmacokinetics / Synthetic opioids / Tandem Mass Spectrometry / Toxicology / Vitreous Body - chemistry / Vitreous humor / Vitreous humour