State-of-the-art of bone marrow analysis in forensic toxicology: a review

Abstract

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

Guidelines for Collection of Biological Samples for Clinical and Forensic Toxicological Analysis

“…Bone marrow: Collect all available for a 10 mL plastic container with screw cap (without preservative); useful in advanced stages of putrefaction since it is protected by bones; high degree of vascularity and lipid content (may accumulate lipophilic xenobiotics); different xenobiotic concentrations are registered in the marrow obtained from the same or different bones [ 24 ]; in xenobiotic distributions are possible [ 20 ]; the label should detail the sampling site; typically, the ribs are cut approximately 5 cm far from its distal end (i.e. near the medioclavicular line) where it is ossified.…”

Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

“…For diazepam, it is known to accumulate in bone marrow and the clearance appears to be slower in bone marrow than in blood. 33 In the study of Imfeld et al, colchicine was still present in the blood when bone concentrations were determined. 30…”

“…In the study of Gorczynski et al , midazolam showed to be present in bone using an enzyme‐linked immunosorbent assay (ELISA), although midazolam was also still detectable in serum. For diazepam, it is known to accumulate in bone marrow and the clearance appears to be slower in bone marrow than in blood . In the study of Imfeld et al , colchicine was still present in the blood when bone concentrations were determined .…”

Issues Affecting Interpretation: Stability and Artefacts

“…Stability of drugs in the bone marrow has predominantly been examined in animal models. Methamphetamine was found to be stable over 2 years when bone samples were stored in a dry environment, whereas opioid levels showed a substantial decrease over a few weeks in buried bones (Cartiser et al 2011). …”