Brain Tissue: A Viable Postmortem Toxicological Specimen

Journal of Analytical Toxicology 2015;39:137 –139 doi:10.1093/jat/bku139 Advance Access publication December 11, 2014 Short Communication Brain Tissue: A Viable Postmortem Toxicological Specimen Timothy P. Rohrig* and Charity A. Hicks Regional Forensic Science Center, 1109 N Minneapolis, Wichita, KS 67214, USA *Author to whom correspondence should be addressed. Email: Brain tissue may be a valuable specimen in interpretation of postmortem toxicology. The protected and isolated position of the brain eliminates or at least attenuates many of the interpretive challenges with postmortem blood specimens. This study presents data for 30 drug and drug metabolites in cases submitted to the Sedgwick County Regional Forensic Science Center for autopsy examination from 2007 to 2014. Drug concentration in heart and femoral blood is compared with the drug concentration in brain tissue. There is a positive correlation of blood to brain concentrations, thus providing another tool for the toxicologist or pathologist to utilize in case interpretation. Introduction The determination of cause and manner of death relies upon scene investigation, medical history, autopsy examination and toxicological analyses. Postmortem specimens that are subjected to toxicological examinations range from bodily fluids to tissues, generally focusing on blood and urine. The interpretive challenges with urine results are that a positive finding only reflects recent exposure, since the bladder is pharmacologically outside the body. Postmortem blood concentrations may not necessarily reflect the drug concentration at the time of death; as drug concentrations may change as a result of body storage conditions, time and site of blood sampling. Although interpretation is possible, it must proceed with caution. Analysis of blood from different anatomical sites and tissue samples may assist in the interpretation of the postmortem results. In many postmortem cases, there is little to no blood for quantitative drug analyses, traumatic injury may lead to significant blood loss or contamination from ruptured stomach contents. The protected and isolated position of the brain may eliminate the challenges of postmortem redistribution (PMR) and delay or attenuate residual enzymatic activity on certain substrates artifactually altering their concentration. Brain tissue is more immune to decomposition allowing for the detection and quantitation in this sample when compared with centrally located organs (e.g., liver) and cavity fluid. Thus, brain tissue has some advantages over other specimens collected at autopsy. Although Baselt (1) has some brain data in individual monographs, overall there is a paucity of data as to the quantitative distribution of drugs into brain tissue. The limited amount of data comparing brain concentrations to paired blood concentrations makes the interpretation difficult when brain tissue is the only viable specimen for testing. It is recognized that a direct quantitative relationship cannot be achieved relating blood concentrations to tissue concentrations. This is due to several factors, the measured drug concentration at the time of death may not reflect complete distribution, that is, acute overdose and/or PMR may skew the relationship. Nonetheless, positive trends or correlations are observed and may assist in the interpretation of the toxicological results, where brain tissue may be the only viable sample for analyses. The aim of this study is to provide additional data on postmortem blood and brain concentrations and thus provide another tool to assist in the interpretation of postmortem toxicological results. Methods The data used for this study were from cases submitted to the Sedgwick County Regional Forensic Science Center (RFSC) for autopsy examination from 2007 to 2014. All causes of death are represented. Cases that were significantly decomposed were not included in the study. The approach was to evaluate the measured drug concentrations in blood (heart or femoral) and compare with the measured brain concentration. Gastric contents were not analyzed. The brain tissue, although not labeled as to the exact anatomical portion of the brain, was generally collected from the cerebrum of the decedent. The quantitative studies were performed using standard validated chromatographic (GC–NPD or GC –MS) methods used during the routine examination of the specimens. No data were taken comparing male to female ratios. Results Table I is a compilation of the results gleaned from the RFSC toxicology case files. The concentrations listed in Table I reflect mean concentrations, with the ranges reflecting the variation of the ratio over the sample size evaluated. Some general trends in drugs belonging to the same structural or pharmacological class are observed in Table I data. Opioids generally tended to have a heart blood concentration that is about half of the brain concentration. Cocaethylene and cocaine, which differ only in a methyl group, have very close heart blood (HB)/brain (Br) values (0.51 and 0.44, respectively). The firstgeneration H1 antagonists chlorpheniramine, promethazine and diphenhydramine have HB/Br values of 0.11, 0.29 and 0.50, respectively. Orphenadrine is classified as an ethanolamine antihistamine, closely related to diphenhydramine, and has an HB/Br of 0.28. Doxylamine, another ethanolamine antihistamine, has an HB/Br of 0.42. Although the sample size is small, there appears to be some overlap in the ratios, which would not be unexpected. Benzoylecgonine (HB/Br 2.27) is a carboxylic acid, and does not readily cross the blood –brain barrier. A lower concentration in the brain than in the blood would be expected. Upon comparison of the mean blood/brain ratio to the median ratio, it was found that they were in general agreement. Hilberg et al. (2) found that with a high volume of distribution, high PMR is expected. This would result in a low HB/Br. This can be seen in Table I with several of the drugs that have a high Vd and also have the expected low HB/Br, such as chlorpheniramine (Vd 3 –6 L/kg, HB/Br 0.11), dextromethorphan (Vd 3.0 L/ kg, HB/Br 0.23), meperidine (Vd 3.7 – 4.2 L/kg, HB/Br 0.25), # The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: Table I Mean Drug Concentration Levels Drug Cases NHB HB (mg/L) Cases NFB FB (mg/L) Brain (mg/kg) HB/Br RangeHB/Br FB/Br RangeFB/Br Vd (L/kg) Alprazolam Amantadine Amphetamine Benzoylecgonine Chlorpheniramine Citalopram Cocaethylene Cocaine Codeine Dextromethorphan Diphenhydramine Doxylamine Fentanyl Hydrocodone Hydromorphone MDPV Memantine Meperidine Methadone Methamphetamine Mirtazapine Morphine Orphenadrine Oxycodone Promethazine Sertraline THC THCA Tramadol Zolpidem 16 0 3 72 1 2 9 43 9 1 14 3 10 125 15 1 1 1 29 2 0 56 1 75 2 4 3 3 4 6 0.0054 – 1.0 1.3 0.3 0.41 0.14 0.39 0.99 2.2 3.0 0.19 0.012 0.29 0.071 0.03 2.1 0.06 0.59 11 – 0.42 1.3 0.35 0.56 1.3 0.067 0.099 (...truncated)