PAPER TOXICOLOGY John F. Wyman, 1,2,  Ph.D.; Dorothy E. Dean, 2 M.D.; Rachel Yinger, 1 B.S.; Amber Simmons, 1 M.S.; David Brobst, 1 B.S.; Michael Bissell, 2 M.D., Ph.D.; Fernando Silveira, 3 D.V.M.; Nancy Kelly 1 ; Robert Shott, 2 M.D.; Joseph Ohr, 1 M.D.; Rick Howard, 3 B.S.; and Bradley Lewis, 1 M.D. The Temporal Fate of Drugs in Decomposing Porcine Tissue* ABSTRACT: Drug levels in decomposed individuals are difficult to interpret. Concentrations of 16 drugs were monitored in tissues (blood, brain, liver, kidney, muscle, and soil) from decomposing pigs for 1 week. Pigs were divided into groups (n = 5) with each group receiving four drugs. Drug cocktails were prepared from pharmaceutical formulations. Intracardiac pentobarbital sacrifice was 4 h after dosing, with tissue collection at 4, 24, 48, 96, and 168 h postdosing. Samples were frozen until assay. Detection and quantitation of drugs were through solid phase extraction followed by gas chromatograph ⁄ mass spectrometer analysis. Brain and kidneys were not available after 48 h; liver and muscle persisted for 1 week. Concentration of drugs increased during decomposition. During 1 week of decomposition, muscle showed average levels increasing but concen- trations in liver were increased many fold, compared to muscle. Attempting to interpret drug levels in decomposed bodies may lead to incorrect conclusions about cause and manner of death. KEYWORDS: forensic science, drugs, decomposing tissue, pig, liver, muscle, blood The distribution of drugs immediately following death (the early postmortem period) and the phenomenon of postmortem redistribu- tion have been well and extensively characterized (1–6). However, postmortem fluids that are routinely collected and analyzed (blood, urine, vitreous humor), and therefore provide the largest compara- tive database for interpretation, are lost as the postmortem interval increases. When bodies have decomposed to the point where no fluids are retrievable, the only specimens available are solid organs and bone. When drugs are found in weathered tissues, there is cur- rently limited information available to help guide the toxicologist, and subsequently the pathologist, in evaluating whether a drug(s) played any significant role in causing the death (1,7,8). The lack of information about the fate of drugs in decomposing tissue is under- standable, in that postmortem studies in humans are not a realistic possibility. This study used pigs as a pharmacological analog to humans and investigated the change in tissue drug levels as decom- position progresses. Decomposing bodies are found in all types of environments, in and out of doors. The design of this study was to monitor concentrations of various drugs, in multiple tissues and organs, during whole body decomposition in the outside environment. The fate of sixteen drugs was followed in seven different tissues collected from decomposing pigs. Specific questions to be answered were: • How do the concentrations of drugs change during tissue decomposition? • How long do drugs and metabolites persist in tissues at detect- able levels? • Which collection sites are most useful for detecting drug expo- sure and interpreting results? Materials and Methods Animal Model A suitable model for this study was Sus domestica, the domestic pig. Pigs were selected because their size is comparable to humans, which allowed high-level dosing and sequential sampling of multi- ple tissues. Also, their similar physiology to that of humans, specif- ically their digestive and cardiovascular physiology (9), allowed for drug absorption and distribution which closely mimic that occurring in humans. The pig has been used previously to study postmortem changes in the concentration of clozapine and norclozapine in blood and tissue (8). The animals used in this study were a York- shire ⁄ Hampshire cross-breed, females and ⁄ or male castrates (as available) and weighed approximately 120–180 pounds (55–82 kg). Pigs were obtained from Kidron Auction, Kidron, OH. The sample size was five animals each ⁄ four drug groups, with four negative controls. To administer drugs (described below), pigs were restrained using a nose snare, and with the aid of a speculum, drug 2011 American Academy of Forensic Sciences 694 Published 2011. This article is a U.S. Government work and is in the public domain in the U.S.A. 1 Franklin County Coroner’s Office, 520 King Ave, Columbus, OH 43201. 2 Department of Pathology, School of Medicine, The Ohio State Univer- sity, 4173 Graves Hall, 3333 10th Ave, Columbus, OH 43210. 3 Department of Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.   Present Address: Cuyahoga County Regional Forensic Science Labora- tory, Cuyahoga County Medical Examiner, 11001 Cedar Ave, Cleveland, OH 44106. *This research was funded by a grant from the Midwest Forensics Resource Center, Ames, IA. Received 2 Sept. 2009; and in revised form 2 Feb. 2010; accepted 2 April 2010. J Forensic Sci, May 2011, Vol. 56, No. 3 doi: 10.1111/j.1556-4029.2011.01725.x Available online at: onlinelibrary.wiley.com