Graham R. Jones

Post-mortem drug redistribution — A toxicological nightmare

Detailed human case data is presented to illustrate the dramatic extent of the phenomenon of post-mortem drug redistribution. The data suggests that there is a post-mortem diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs, into the blood with resultant artefactual elevation of drug levels in blood. Highest drug levels were found in central vessels such as pulmonary artery and vein, and lowest levels were found in peripheral vessels such as subclavian and femoral veins. In individual cases, in multiple blood samples obtained from ligated vessels, concentrations of doxepin and desmethyldoxepin ranged from 3.6 to 12.5 mg/l and 1.2 to 7.5 mg/l, respectively; amobartital, secobarbital and pentobarbital from 4.3 to 25.8 mg/l, 3.9 to 25.3 mg/l and 5.1 to 31.5 mg/l respectively; clomipramine and desmethylclomipramine from 4.0 to 21.5 mg/l and 1.7 to 8.1 mg/l, respectively and flurazepam 0.15 to 0.99 mg/l; imipramine and desipramine from 4.1 to 18.1 mg/l and 1.0 to 3.6 mg/l, respectively. We conclude that this poorly studied phenomenon creates major difficulties in interpretation and undermines the reference value of data bases where the site of origin of post-mortem blood samples is unknown.

Acute Fatal Acetaminophen Overdose Without Liver Necrosis

Abstract:  Two unusual cases of suicidal overdose of acetaminophen (paracetamol) without the usual extensive centrilobular necrosis of the liver are reported. Both cases were subjected to comprehensive drug screening by immunoassay, and a combination of gas chromatography with mass spectrometry, nitrogen detection, and electron capture detection. Acetaminophen was detected in both cases. No other drugs were detected in case #1, and only a small amount of olanzapine (<0.1 mg/L) was detected in case #2. No anatomical cause of death was identified in either case. If untreated, the normal outcome of a large acetaminophen overdose would be massive hepatic necrosis with delayed death and low blood and tissue acetaminophen concentrations. In contrast, particularly high postmortem acetaminophen concentrations were measured in both our cases with little hepatic tissue damage. For case #1, femoral blood acetaminophen 1280 mg/L, vitreous 878 mg/L, and liver 729 mg/kg; in case #2, cardiac blood 1220 mg/L, vitreous 779 mg/L, liver 3260 mg/kg, and gastric 11,500 mg/500 g. Acetaminophen was measured using high performance liquid chromatography with UV detection (254 nm) using 3‐hydroxyacetanilide as the internal standard. The very high concentrations of acetaminophen is these cases but relatively little hepatic damage suggests an alternative, possibly cardiac, mechanism of death.

A Case of Fatal Benzylpiperazine (BZP) and Trifluoromethylphenylpiperazine (TFMPP) Toxicity

Abstract Toxicology analysis carried out on several postmortem samples relating to the sudden death of a 21-year-old male, confirmed the presence of high concentrations of N-benzylpiperazine (BZP) and 3-trifluoromethylphenylpiperazine (TFMPP). Methamphetamine (MA), 3,4-methylenedioxy- methylamphetamine (MDMA, ‘Ecstasy’) and trace amounts of 3,4-methylenedioxyamphetamine (MDA) and amphetamine were also detected. Items examined included femoral blood, vitreous, urine, liver, bile and gastric contents, which were all obtained during a postmortem examination that was carried out within 24 hours of the discovery of the body. A number of brightly coloured tablets (recovered from the scene) were also analysed and were found to contain primarily BZP and TFMPP. One type of tablet additionally contained MA. Postmortem blood and other specimens analysed by GC/MS with selected ion monitoring using TFMPP-d4 as the internal standard, gave the following results: BZP: femoral blood 21.4, vitreous 25.2, liver 120, bile, 200, gastric 80; TFMPP femoral blood 3.3, vitreous 1.7, urine 90, liver 84, bile 61 and gastric 37 (all results mg/L except liver mg/kg and gastric mg/78.1 g). Femoral blood also contained 0.22 mg/L of MA and 0.26 mg/L MDMA.

Drugs-of-Abuse in Liver

The liver is the largest organ in the human body and has been used extensively as an important specimen in postmortem toxicology analysis. This chapter describes the advantages and disadvantages of using liver as a specimen for the detection and measurement of drugs-of-abuse in postmortem cases. The liver comprises relatively soft tissue amenable to the preparation of homogenates but contains high concentrations of lipids that may interfere in some analytical procedures. As a specimen, liver has the advantage that it is relatively unaffected by postmortem redistribution compared with blood, but drug concentrations in the lobe proximal to the stomach may be affected by postmortem diffusion in cases of oral overdose. The biggest impediment to the routine use of liver for the interpretation of positive drug findings is the lack of a comprehensive database of liver concentrations. The data contained here may assist those wishing to interpret liver concentrations of drugs-of-abuse. As for all drugs and specimens, the process of interpretation should include consideration of all aspects of the death investigation, including, as necessary, analysis of multiple specimens.