Characterization of drug disposition in skeletal tissues - a forensic context

在许多臭名昭著的死亡调查中，被调查的遗体已经腐烂到部分或完全只剩骨架的地步。在这种情况下，阐明药物或毒药在导致死亡或与死亡有关的事件中的作用极具挑战性。通常对血液或尿液等液体或肝脏等组织进行的常规毒理学分析通常是不可能的。在这些情况下，分析骨组织（矿化骨和/或骨髓）可能是唯一剩下的选择。本研究计划将通过在法医环境下骨骼组织中药物浓度的表征来解决这个问题。采用动物模型研究不同给药条件、骨类型和死后环境条件下骨组织中药物浓度的变化。将检查不同的法医相关药物，以更好地了解药物的化学性质的变化对骨组织中观察到的浓度的影响。这项研究的结果将提供深入了解暴露在骨组织中多长时间可以检测到给定药物，死后骨组织中药物的稳定性，暴露于给定剂量后预期的骨药物浓度范围以及骨骼药物分析的最佳骨骼类型和特定骨骼中的位置。这项工作为扩展人体组织的研究奠定了基础。一旦收集到这些数据，就可以开始将其应用于司法系统内的有关案件。

In many notorious death investigations, the remains under investigation have decomposed to the point of partial or complete skeletonization. In such cases, elucidating the role of drugs or poisons in the events leading up to or associated with the death is extremely challenging. Conventional toxicological analyses, usually done on fluids such as blood or urine, or tissues such as liver, are often not possible. In these cases, analysis of skeletal tissues (mineralized bone and/or bone marrow) may be the only remaining option.  This research program will address this problem through characterization of drug concentrations in skeletal tissues in a forensic context.Animal models will be used to investigate the concentration of drug in bone tissue under various conditions of drug administration, bone type and postmortem environmental conditions. Different drugs of forensic relevance will be examined to better understand the effect of variations in the chemical properties of the drugs on the observed concentration in bone tissue. The results of this research will provide insight into how long after exposure a given drug may be detected in bone tissue, the stability of drugs within postmortem skeletal tissues, bone drug concentration ranges expected following exposure to a given dose as well as the optimal bone type, and location within a particular bone, for skeletal drug analysis. This work serves as a basis for extension to studies with human tissues. Once this data has been collected, work may begin in its application to relevant cases within the justice system.