The effect of the postmortem interval on the redistribution of drugs: a comparison of mortuary admission and autopsy blood specimens.

Postmortem redistribution (PMR) is an accepted toxicological phenomenon that may affect the interpretation of postmortem blood concentrations. The extent of PMR is not well understood for some drugs. This report describes the PMR of selected substances resulting from the analysis of 149 cases comparing blood specimens taken at admission of the deceased to the mortuary and then at autopsy. Blood was collected in preserved tubes containing 1 % sodium fluoride/potassium oxalate. All cases were subject to a full autopsy and blood extracts were analyzed using a targeted screen by LC-MS/MS. 30 drug or drug metabolites that were detected with an incidence of 6 or more were included in this study. The pre-autopsy interval ranged from 0.5 to 164 h (6.4 days) with an average of 64 h for the cases analyzed. The increase in drug concentration from mortuary admission to autopsy ranged from 30 % for drugs such as citalopram, mirtazapine, and sertraline to 300 % for doxylamine. Only 7 drugs of the 30 studied showed increases of greater than 20 % when comparing autopsy to mortuary admission blood irrespective of the length of the postmortem interval. Drugs including methadone, EDDP, fluoxetine, mirtazapine, and sertraline all showed statistically significant increases during the pre-autopsy interval (p < 0.05) while 6-acetylmorphine, 9-hydroxy-risperidone, and caffeine showed significant decreases (p < 0.05) from mortuary admission to autopsy. While femoral blood is thought to reduce PMR, this data shows that for some drugs significant redistribution can occur even when taking peripheral specimens irrespective of the delay in the postmortem interval.

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.