The results suggest that there is a wide range in gastric emptying in critically ill patients. The results may be due to the case mix of the patients. The use of dopamine may adversely affect gastric emptying and requires further investigation in the ICU patient. Prediction of gastric emptying is difficult in these patients and further investigation is necessary in order to improve our understanding of this process.

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The analytical toxicologist may be required to detect, identify, and in many cases measure a wide variety of compounds in samples from almost any part of the body or in related materials such as residues in syringes or in soil. This book gives principles and practical information on the analysis of drugs and poisons in biological specimens, particularly clinical and forensic specimens. After providing some background information the book covers aspects of sample collection, transport, storage and disposal, and sample preparation. Analytical techniques - colour tests and spectrophotometry, chromatography and electrophoresis, mass spectrometry, and immunoassay - are covered in depth, and a chapter is devoted to the analysis of trace elements and toxic metals. General aspects of method implementation/validation and laboratory operation are detailed, as is the role of the toxicology laboratory in validating and monitoring the performance of point of care testing (POCT) devices. The book concludes with reviews of xenobiotic absorption, distribution and metabolism, pharmacokinetics, and general aspects of the interpretation of analytical toxicology results. A clearly written, practical, integrated approach to the basics of analytical toxicology. Focuses on analytical, statistical and pharmacokinetic principles rather than detailed applications. Assumes only a basic knowledge of analytical chemistry. An accompanying website provides additional material and links to related sites. Written by an experienced team of authors,Fundamentals of Analytical Toxicology is an invaluable resource for those starting out in a career in analytical toxicology across a wide range of disciplines including clinical and forensic science, food safety, and pharmaceutical development. © 2007 John Wiley & Sons, Ltd

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The biodistribution of temoporfin (tetra[m-hydroxyphenyl]chlorin, m-THPC), a recently developed photosensitizer, was investigated in BALB/c mice. The drug was administered intravenously (0.35-0.75 mumol/kg) to tumor-free mice or to mice implanted with the Colo 26 colorectal carcinoma. Blood and tissue samples were collected for up to 96 h post-dose. Drug concentrations were determined by HPLC coupled to photometric detection at 423 nm. Concentrations in blood and liver fell relatively rapidly such that blood concentrations at later time points were below the limit of detection. Tumor concentrations rose at first and then remained constant from 24 h. Temoporfin concentrations in some tissues, notably heart and skeletal muscle, declined only slowly when compared to blood. The tumor: tissue ratios for those organs that showed a more rapid decline in temoporfin concentrations were higher at later times, whereas in tissues such as muscle the ratio remained relatively constant. The organs with the highest tumor:tissue ratios were small intestine (8.6), liver (6.9) and skeletal muscle (5.0).

Rectal cisapride in the dose given achieved average plasma concentrations similar to those concentrations achieved in healthy subjects after 30 mg of cisapride rectally. There is a large variation in gastric emptying from one day to the next and large numbers of patients are required to determine if cisapride administration improves early gastric emptying in critically ill patients. The volume of gastric aspirate and the presence of bowel sounds do not correlate with gastric emptying.

This paper discusses new developments in plasma micro-extraction techniques in the context of established micro-extraction and protein precipitation methodology. Simple liquid-liquid solvent extraction (LLE) of plasma with direct GC or HPLC analysis of the resulting extract has been used for many years. Butyl acetate and methyl t-butyl ether (MTBE) give efficient extraction of many drugs and metabolites from small volumes of plasma or whole blood at an appropriate pH, and form the upper layer, thus simplifying extract removal. Butyl acetate does not interfere with NPD, ECD or MS in GC, whilst MTBE has a relatively low UV cutoff (220 nm). Thus, HPLC eluents that use a high proportion of an organic component allow MTBE extracts to be analysed directly. 'Salting-out' and extractive derivatization using acetic anhydride or phenylboronic acid can be used with appropriate analytes. As regards protein precipitation, an important consideration is lowering the pH, although this is not feasible with acid-labile analytes. More recent developments include sold-phase micro-extraction (SPME) and liquid-phase micro-extraction (LPME). This latter technique especially may prove invaluable as analytes that cannot easily be extracted with LLE can be isolated simply at low cost with a minimum of apparatus.

Release of excitatory amino acids and dopamine plays a central role in neuronal damage after cerebral ischaemia. In the present study, we used an in vitro model of ischaemia to investigate the effects of sevoflurane on dopamine, glutamate and aspartate efflux from rat corticostriatal slices. Slices were superfused with artificial cerebrospinal fluid at 34 degrees C and episodes of 'ischaemia' were mimicked by removal of oxygen and reduction in glucose concentration from 4 to 2 mmol litre(-1) for < or = 30 min. Dopamine efflux was monitored in situ by voltammetry while glutamate and aspartate concentrations in samples of the superfusate were measured by HPLC with fluorescence detection. Neurotransmitter outflow from slices was measured in the absence or presence of sevoflurane (4%). After induction of ischaemia in control slices, there was a mean (SEM) delay of 166 (7) s (n = 5) before sudden efflux of dopamine which reached a maximum extracellular concentration of 77.0 (15.2) micromol litre(-1). Sevoflurane (4%) reduced the rate of dopamine efflux during ischaemia (6.90 (1.5) and 4.73 (1.76) micromol litre(-1) s(-1) in controls and sevoflurane-treated slices, respectively; P<0.05), without affecting its onset or magnitude. Excitatory amino acid efflux was much slower. lschaemia-induced glutamate efflux had not reached maximum after 30 min of ischaemia. Basal (pre-ischaemic) glutamate and aspartate efflux per slice was 94.8 (24.8) and 69.3 (31.5) nmol litre(-1) superfusate (n = 4) and was not significantly reduced by 4% sevoflurane. lschaemia greatly increased glutamate and aspartate efflux (to a maximum of 919 (244)% and 974 (489)% of control, respectively). However, ischaemia-induced efflux of both glutamate and aspartate was significantly reduced by 4% sevoflurane (P < 0.001 for glutamate, P < 0.01 for aspartate). In summary, sevoflurane may owe part of its reported neuroprotective effect to a reduction of ischaemia-induced efflux of excitatory amino acids and, to a lesser extent, dopamine.