Publications by authors named "Steve Silvester"

Rising population density and global mobility are among the reasons why pathogens such as SARS-CoV-2, the virus that causes COVID-19, spread so rapidly across the globe. The policy response to such pandemics will always have to include accurate monitoring of the spread, as this provides one of the few alternatives to total lockdown. However, COVID-19 diagnosis is currently performed almost exclusively by reverse transcription polymerase chain reaction (RT-PCR).

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In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 h post-fertilization. Chemicals' distribution is modeled in the cells, lysosomes, and mitochondria of ten organs of the embryo. The model's partition coefficients are calculated with sub-models using physicochemical properties of the chemicals of interest.

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Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the 'migration-inhibition of NCC (cMINC)' assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate.

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Background: The aim of the work described herein was to undertake a systematic investigation of the effect of mobile phase pH and organic modifier in typical reversed-phase LC-MS methods with regard to ESI-MS response, chromatographic performance and correlation of retention time with in silico logD predictions.

Results: For the test set of pharmaceutical analytes investigated, ESI-MS response was generally greater when employing methanol rather than acetonitrile as the organic modifier, and increases of up to tenfold were observed dependent on the pH-buffered mobile phase employed. Deleterious effects on chromatographic performance of protonated basic analyte were observed under conditions of neutral to weakly basic pH.

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Background: Endogenous phospholipids have a profound matrix effect in bioanalytical LC-MS methods and considerable effort is invested in strategies to minimize their impact either by removal during sample processing or chromatographic separation during the analytical run. The aim of the research presented in this article was to investigate the latter approach, under reversed-phase conditions.

Results: The retention of glycerophosphocholines (GPCs) in mobile phases employing acetonitrile demonstrated a complex 'U-shaped' relationship with the percentage of organic.

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A key challenge in the development of robust bioanalytical methods, for the determination of drug analyte in human urine samples, is the elimination of potential analyte losses as a result of non-specific adsorption to container surfaces in which the samples are collected, stored or processed. A common approach to address adsorption issues is to treat the urine samples with additives that serve to increase analyte solubility and/or minimise interaction with the container surfaces. A series of adsorption experiments were performed on human urine samples containing an adsorption-prone in-house development compound (AZD9164).

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The 6th Annual Bioanalysis in Clinical Research conference held recently in London, UK, targeted numerous themes of significant current interest within the discipline of bioanalysis. The conference invited a diverse speaker panel and attracted an audience consisting of researchers from the pharmaceutical industry, CROs and academia. The range of topics presented covered LC-MS and ligand-binding assays, small- and large-molecule quantification, regulatory issues and concerns and new technologies.

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