Aims-To compare blood drug concentrations during life with postmortem drug concentrations measured from a peripheral site and a central site. Methods-Coroner's cases from October 1990 to July 1997 were reviewed. Six cases had data on both antemortem and postmortem blood drug concentrations. The postmortem to antemortem ratio was compared with the postmortem central to peripheral ratio, using cardiac blood as a central site and femoral blood as a peripheral site. Results-Drugs that have a high postmortem central to peripheral ratio; that is, drugs that exhibit considerable postmortem redistribution, also have high postmortem to antemortem ratios. Conclusions-A large degree of error can arise from attempting to estimate antemortem drug concentrations and the ingested dose from postmortem measurements. The chosen site and technique for postmortem blood sampling can greatly influence the concentration of drug measured. (J Clin Pathol 2000;53:282-285) Keywords: postmortem blood sampling; drug concentrations; toxicological analysis Postmortem drug redistribution refers to the processes by which the movement of drugs and other chemical poisons between tissues, organs, and body fluids takes place after death. This phenomenon is well recognised, and was first reported 25 years ago.1 Since then, considerable eVort has gone into elucidating the processes responsible.2-16 Consideration of the redistribution of drugs is important in a variety of situations. Cases of suspected poisoning, either homicidal or suicidal; the role of drugs in "marginally toxic" cases, such as vehicle accidents; and also potential cases of euthanasia or medical negligence might rely upon the toxicological analysis of blood samples.2 The timing, method of collection, and source of the sample might influence the interpretation of toxicological analyses.The processes of postmortem redistribution result in the migration of drugs between blood and tissues. The rate and extent of this movement varies according to several factors, including the nature of the drug and the time interval between death and postmortem specimen collection. Within the torso, the major organs constitute potential drug pools, and the gastrointestinal tract might contain considerable quantities of unabsorbed drug, and thus central blood is subject to redistribution from these local organs. Peripheral blood, such as femoral blood, is subject to redistribution influences only from local tissues-muscle and fat. In general, redistribution into central vessels is greater than redistribution into peripheral vessels. The diVerence between the two sites is known as the central to peripheral (C/P) ratio. For these reasons, the blood specimen of choice for toxicological analysis after death is a femoral venous sample, ideally collected from a ligated vessel, 7 10 although inevitably there will be situations in which such sample collection is not possible.Often, pathologists or toxicologists are requested to estimate the amount of drug present at the time of death, or the number of...

An analytical database, using high-performance liquid chromatography (HPLC) with diode array ultraviolet (UV) detection, of over 250 toxicologically relevant drugs has been extensively applied to both clinical and forensic toxicology. This general drug screening system, based on a mixed-phase (octadecyl/cyanopropyl) column and gradient reversed-phase HPLC, can identify a wide range of basic, acidic, and neutral drugs and metabolites, some of which are not amenable to gas chromatography and thin-layer chromatography. Compounds are identified using both retention index (RI) value (calculated by interpolation between a series of reference drug markers) and UV spectral data. It has been previously shown that this chromatographic system provides long-term reproducibility and has potentially useful selectivity differences compared with those based on octadecylsilane columns. Development has been undertaken to improve the speed and practicality of the system for emergency toxicology screening by increasing the rate of the elution gradient, while maintaining the applicability of the RI database. The database has also been found to be an important tool in determining optimum strategies for the adaptation of the system for quantitative analyses of drugs and metabolites under isocratic conditions.

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SUMMARY. Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses O·5 mL plasma, is linear to 10 mg/L and had a detection limit of O·2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.

High-performance liquid chromatography-diode-array detection results obtained during the investigation of two cases involving acepromazine prompted us to study the stability of the drug in blood. It was found that acepromazine can undergo in vitro conversion by human red blood cells to 2-(1-hydroxyethyl)promazine, a product that has been reported as a minor urinary metabolite in horse urine but not previously identified in humans. Further, our analytical findings in the two cases examined suggest that 2-(1-hydroxyethyl)promazine may be the major unconjugated metabolite of acepromazine in humans. These findings have important implications for the analytical toxicology of acepromazine.