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...

ABSTRACT:In vitro biosynthesis using pooled human liver microsomes was applied to help identify in vivo metabolites of ketamine by liquid chromatography (LC)-tandem mass spectrometry. Microsomal synthesis produced dehydronorketamine, seven structural isomers of hydroxynorketamine, and at least five structural isomers of hydroxyketamine. To aid identification, stable isotopes of the metabolites were also produced from tetra-deuterated isotopes of ketamine or norketamine as substrates. Five metabolites (three hydroxynorketamine and two hydroxyketamine isomers) gave chromatographically resolved components with product ion spectra indicating the presence of a phenolic group, with phenolic metabolites being further substantiated by selective liquid-liquid extraction after adjustments to the pH. Two glucuronide conjugates of hydroxynorketamine were also identified. Analysis by LCcoupled ion cyclotron resonance mass spectrometry gave unique masses in accordance with the predicted elemental composition. The metabolites, including the phenols, were subsequently confirmed to be present in urine of subjects after oral ketamine administration, as facilitated by the addition of deuterated metabolites generated from the in vitro biosynthesis. To our knowledge, phenolic metabolites of ketamine, including an intact glucuronide conjugate, are here reported for the first time. The use of biologically synthesized deuterated material as an internal chromatographic and mass spectrometric marker is a viable approach to aid in the identification of metabolites. Metabolites that have particular diagnostic value can be selected as candidates for chemical synthesis of standards.

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The popularity of traditional remedies has greatly increased in westernised countries over recent years. Although many of these remedies are used safely, there have recently been an increasing number of case reports being published of heavy metal poisoning after the use of traditional remedies, in particular, Indian Ayurvedic remedies. This study reviews the data on published cases, along with the history of Ayurvedic medicine in an attempt to provide an insight into why heavy metals, in particular lead, mercury and arsenic are added in such large concentrations to these remedies.

Due to its closed ring system, 2-aminoindane is a conformationally rigid analogue of amphetamine. Internet websites offering synthetic compounds as 'research chemicals' have recently been advertising 5,6-methylenedioxy-2-aminoindane (MDAI), 5, 6-methylenedioxy-N-methyl-2-aminoindane (MDMAI), 5-iodo-2-aminoindane (5-IAI), and 5-methoxy-6-methyl-2-aminoindane (MMAI). The chemistry, pharmacology, and toxicological aspects of this new class of psychoactive substances are reviewed, as these could become the next wave of 'legal highs'.

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