Distribution of drugs and toxic chemicals in blood.
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Biomedical subjects
Publications and source records attributed to M D Osselton.
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1. Citreoviridin was a potent inhibitor of the soluble mitochondrial ATPase (adenosine triphosphatase) similar to the closely related aurovertins B and D. 2. Citreoviridin inhibited the following mitochondrial energy-linked reactions also: ADP-stimulated respiration in whole mitochondria from ox heart and rat liver; ATP-driven reduction of NAD+ by succinate; ATP-driven NAD transhydrogenase and ATPase from ox heart submitochondrial particles. 3. The dissociation constant (KD) calculated by a simple law-of-mass-action treatment for the citreoviridin--ATPase complex was 0.5--4.2micron for ox-heart mitochondrial preparations and 0.15micron for rat liver mitochondria. 4. Monoacetylation of citreoviridin decreased its inhibitory potency (KD=2--25micron, ox heart; KD=0.7micron, rat liver). Diacetylation greatly decreased the inhibitory potency (KD=60--215micron, ox heart). 5. Hydrogenation of citreoviridin monoacetate diminished its inhibitory potency considerably. 6. No significant enhancement of fluorescence was observed when citreoviridin interacted with the mitochondrial ATPase.
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A simple, rapid and sensitive method is described for the analysis of unchanged benzodiazepine drugs and their metabolites, in human and animal tissues, using the proteolytic enzyme subtilisin Carlsberg followed by reverse-phase liquid chromatography. The enzymic digestion yields far higher recoveries than conventional extraction methods, while the liquid chromatogrpahic analysis allows the rapid separation and detection of nanogram quantities of these drugs without the need for elaborate "clean-up" procedures.
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The problems associated with the handling and storage of blood samples for the analysis of toluene in toxicological casework using headspace gas chromatography have been investigated. Significant losses of toluene and the internal standard, ethylbenzene, from solution may be observed during handling. Toluene may be lost into the headspace above the blood in a storage container while such headspaces can also be detrimental, leading to the formation of n-hexanal, a possible interference with the assay. Large differences in the stability of toluene were seen for blood samples in different types of storage container. Storage containers in which the sample was only in contact with glass, teflon, or aluminum foil were most satisfactory. It is recommended that blood samples should be stored in appropriate containers with minimum headspace under cold conditions (4 degrees C). Transfers of blood should also be made at cold temperatures. The applicability of these guidelines to the analysis of other volatile compounds is discussed.
Part I. Expert 4: The object of this study was to investigate the applicability of commercially available expert system shells to interpretation in forensic toxicology. Amitriptyline toxicology was selected as a pilot trial. Blood and tissue concentrations of amitriptyline and nortriptyline in fatal and nonfatal amitriptyline cases from the literature and from the Registry of Human Toxicology databank were entered into the expert system shell Expert 4 (Rivers, Elsevier). The statistical evaluation routines of the shell were used to search for patterns in the data. Successive changes in the data base were made to test for the influence of the data base on the conclusions. Finally the data base was refined, based on the evaluations, to strengthen the probabilities of the conclusions. The refined database was coupled with the Expert 4 inference engine to infer unknown parameters in the cases. The results of the expert system analysis were compared to known values and published expert opinions. The ratio of amitriptyline/nortriptyline and tissue levels of nortriptyline were found to be the most significant measures for interpretation of effect and time since ingestion. Part II. Computer Induction of Rules: Blood and tissue concentrations of amitriptyline and nortriptyline in fatal and nonfatal amitriptyline cases from the literature and from the Registry of Human Toxicology databank were entered into the expert system shell BEAGLE, (Forsyth, Machine Learning Research, Ltd.). The automatic rule induction routines of the shell were used to search for patterns in the data. The program expressed these patterns as numerical predictions or Boolean logic rules. The results were compared to those obtained with the Expert 4 (Rivers, Elsevier) using the same case knowledge base.(ABSTRACT TRUNCATED AT 250 WORDS)
A variety of liquid-liquid and solid-phase extraction techniques have been compared for the extraction of tricyclic antidepressant drugs from small whole blood samples. Each of the procedures was evaluated with respect to extract cleanliness, extraction efficiency, and reproducibility. The three most efficient methods were compared on a variety of authentic whole blood case samples containing drugs at therapeutic and toxic levels. The results of the study indicated that a liquid-liquid extraction procedure involving the extraction of drugs by ether was the most suitable to use on poor quality forensic samples.
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Pilot studies were undertaken to examine the feasibility of preparing freeze-dried whole blood samples containing drugs of interest to be used as assay controls. The availability of such samples will enable analysts and laboratory managers to monitor analytical performance. A pilot batch of freeze-dried blood containing five compounds of forensic significance and a blank blood sample were prepared for reconstitution to 2.5-mL aliquots. Samples of each of these preparations were distributed to 55 laboratories in the USA and UK for analysis. A summary of the results is presented along with comments on the feasibility of producing freeze-dried whole blood samples for use in forensic toxicology.