|Monday, August 25||Postmortem Analysis and Drug Stability|
STABILITY OF DRUGS POSTMORTEM: A REVIEW|
Correct interpretation of forensic toxicological results is very much dependent on an assessment of any competing processes. Most significant in any assessment is knowledge concerning the stability of drugs and poisons in biological matrices. Instability can derive from chemical and physical, or metabolic processes.
Substances capable of attack by esterases are rapidly altered postmortem. Examples include heroin, cocaine, acetylsalicylic acid, most prodrugs including those of the benzodiazepines. Deacetylation of heroin and 6-monoacetylmorphine will lead to an elevation of unconjugated morphine concentrations after death. Toxicologists must therefore target the right substance in order to best adjust for these processes.
Many of the benzodiazepines show losses that can be attributed to a combination of chemical degradation and metabolic attack. For example, the nitrobenzodiazepines such as flunitrazepam are rapidly converted to the 7-amino form. This occurs by enzymes found in bacteria associated with postmortem blood. This is inhibited by fluoride, but can also occur spontaneously which is not inhibited by fluoride. The instability of other benzodiazepines are known although the mechanism of loss is still poorly understood.
Sulphur-containing drugs such as thioridazine are unstable postmortem and are converted, in part, to the sulfoxide and sulfone forms. This conversion is variable and not predictable, and leads to a change in the ratio of parent drug to metabolite which can lead to errors in differentiating acute from chronic exposure. This even occurs in blood samples frozen at -20° C. Biological specimens must therefore be taken to minimise any bacterial contamination, contain preservatives such as fluoride and be frozen to less than -20° C to reduce losses.
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