Neil Spooner

Bio: Neil Spooner is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Dried blood spot & Bioanalysis. The author has an hindex of 30, co-authored 56 publications receiving 3480 citations. Previous affiliations of Neil Spooner include University of Hertfordshire & Northeastern University.

Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method.

Abstract: A novel approach has been developed for the quantitative determination of circulating drug concentrations in clinical studies using dried blood spots (DBS) on paper, rather than conventional plasma samples. A quantitative bioanalytical HPLC-MS/MS assay requiring small blood volumes (15 microL) has been validated using acetaminophen as a tool compound (range 25 to 5000 ng/mL human blood). The assay employed simple solvent extraction of a punch taken from the DBS sample, followed by reversed phase HPLC separation, combined with selected reaction monitoring mass spectrometric detection. In addition to performing routine experiments to establish the validity of the assay to internationally accepted criteria (precision, accuracy, linearity, sensitivity, selectivity), a number of experiments were performed to specifically demonstrate the quality of the quantitative data generated using this novel sample format, namely, stability of the analyte and metabolites in whole human blood and in DBS samples; effect of the volume of blood spotted, the device used to spot the blood, or the temperature of blood spotted. The validated DBS approach was successfully applied to a clinical study (single oral dose of 500 mg or 1 g acetaminophen).

Volumetric absorptive microsampling: a dried sample collection technique for quantitative bioanalysis.

Abstract: Volumetric absorptive microsampling (VAMS) is a novel approach to obtaining a dried blood sample for quantitative bioanalysis that overcomes the area bias and homogeneity issues associated with conventional dried blood spot (DBS) sample when a subpunch is taken. The VAMS sampler absorbs a fixed volume of blood (∼10 μL) in 2–4 s with less than 5% volume variation across the hematocrit range of 20–70% with low tip-to-tip variability. There is no evidence of selective absorption by the tip of the plasma component over whole blood. Recommendations for best practice when collecting samples were developed based upon the results of tests examining a number of potential abuse scenarios.

The effect of hematocrit on assay bias when using DBS samples for the quantitative bioanalysis of drugs

Abstract: Background: As hematocrit levels are known to vary between individuals and with disease state, its effect on the physical characteristics of dried blood spot (DBS) samples and on the accurate quantification of analytes within these samples is examined. Results: The area of DBS samples decreases with increasing hematocrit levels in a linear manner on the three cellulose paper substrates tested. Furthermore, a bias was observed in the concentrations of two analytes determined in DBS samples at different hematocrits, which in some cases exceeded acceptable values, particularly for hematocrits outside normal values. Conclusion: If it is expected that the hematocrit of study samples will vary from values considered normal, then its effect on the quantitative determination of an analyte in DBS samples should be investigated as part of the method development and validation. If an unacceptable effect is observed, then this will need to be addressed, by modification of the analytical method, or the inclusion of qu...

Guidelines for the welfare and use of animals in cancer research

Abstract: Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.

Ecotoxicology of organotin compounds.

Abstract: Organotin compounds are ubiquitous contaminants in the environment. The high biological activity of some compounds toward aquatic organisms lead to deleterious impacts in aquatic ecosystems. Here, the aquatic ecotoxicology of organotins is reviewed based on a multidisciplinary approach involving environmental chemical, toxicological, and ecological aspects. Basic results were obtained both with field and laboratory studies, and some of the most important recent results and conclusions are critically reviewed. The contamination of and fate in aquatic systems is reported and linked with effects at different levels of biological organization. Major emphasis is placed on the development of a concept of ecotoxicology that encompasses not only effect assessment alone, but also integrates environmental chemistry with aquatic toxicology. Thereby, the influence of speciation for bioavailability, basic modes of toxic action, and aquatic toxicity are discussed. This case study on organotins allows to a certain extent generalizations to ecotoxicology in general.

Plant sterols: biosynthesis, biological function and their importance to human nutrition.

Abstract: Plant sterols are an essential component of the membranes of all eukaryotic organisms. They are either synthesised de novo or taken up from the environment. Their function appears to be to control membrane fluidity and permeability, although some plant sterols have a specific function in signal transduction. The phytosterols are products of the isoprenoid pathway. The dedicated pathway to sterol synthesis in photosynthetic plants occurs at the squalene stage through the activity of squalene synthetase. Although the activity of 3-hydroxymethyl-3-glutaryl coenzyme A (HGMR) is rate-limiting in the synthesis of cholesterol, this does not appear to be the case with the plant sterols. Up-regulation of HGMR appears to increase the biosynthesis of cycloartenol but not the Δ5-sterols. A decline in sterol synthesis is associated with a suppression of squalene synthetase activity, which is probably a critical point in controlling carbon flow and end-product formation. The major post-squalene biosynthetic pathway is regulated by critical rate-limiting steps such as the methylation of cycloartenol into cycloeucalenol. Little is known about the factors controlling the biosynthesis of the end-point sterol esters or stanols. The commonly consumed plant sterols are sitosterol, stigmasterol and campesterol which are predominantly supplied by vegetable oils. The oils are a rich source of the steryl esters. Less important sources of sterols are cereals, nuts and vegetables. The nutritional interest derives from the fact that the sterols have a similar structure to cholesterol, and have the capacity to lower plasma cholesterol and LDL cholesterol. Since the morbidity and mortality from cardiovascular disease have been dramatically reduced using cholesterol-lowering drugs (statins), the interest in plant sterols lies in their potential to act as a natural preventive dietary product. Stanols (saturated at C-5) occur in low amounts in the diet and are equally effective in lowering plasma cholesterol and do not cause an increase in plasma levels, unlike the sterols which can be detected in plasma. © 2000 Society of Chemical Industry