Drugs in formalin-fixed specimens - a review on reactivity and stability

Formalin-fixed specimens represent particular challenges in the field of forensic toxicology. Despite being a rare occurrence, the circumstances of certain cases may require toxicological analyses of embalmed or fixed tissues. However, the preservation causes a variety of physical and chemical processes influencing the concentration and the detectability of many target analytes. While redistribution of drugs between tissue and formaldehyde solution may be reflected in measuring both tissue and fixing solution concentrations, reactions of target analytes with formaldehyde may lead to more complex behavior of drugs. Some of those degradation pathways have been comprehensively described, e.g. Eschweiler-Clarke conversion of amines. Considering both the redistribution and reactions of drugs in fixed specimens, most toxicologically relevant substances can be detected, either directly or by identifying specific degradation products. This review summarizes the current knowledge of drug-formaldehyde reactions and documents the stability of a broad variety of drugs.