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Wilson C.G.,Strathclyde Institute of Pharmacy and Biomedical science
International Journal of Pharmaceutics | Year: 2010

Colonic transit is a subject of great relevance when considering in vivo/. in vitro relationships for oral controlled release dosage forms. Our knowledge of colonic motility has first come from the clinic, where measurement of the whole gut transit of different excreted markers was used as a method of discriminating pathologies. X-ray contrast, although widely available, was used sparing due to the accumulating dosimetry associated with each exposure. Although such methods were used for swallowing studies, gamma scintigraphy allowed physicians to measure colon function with a more moderate radiation burden. The ability to label meal and dosage form separately and to measure dispersion with more certainty, prompted the use in pharmaceutical sciences; finally, the relationship between blood concentrations and transit of different sized dosage began to be understood. This mini-review considers the development of colon transit measurements and how different designs of clinical assessment assist in elucidating size and shape influence on colon transit in man. © 2010 Elsevier B.V. Source


Watson D.G.,Strathclyde Institute of Pharmacy and Biomedical science
Computational and Structural Biotechnology Journal | Year: 2013

Compound identification in mass spectrometry based metabolomics can be a problem but sometimes the problem seems to be presented in an over complicated way. The current review focuses on metazoans where the range of metabolites is more restricted than for example in plants. The focus is on liquid chromatography with high resolution mass spectrometry where it is proposed that most of the problems in compound identification relate to structural isomers rather than to isobaric compounds. Thus many of the problems faced relate to separation of isomers, which is usually required even if fragmentation is used to support structural identification. Many papers report the use of MS/MS or MS2 as an adjunct to the identification of known metabolites but there a few examples in metabolomics studies of metazoans of complete structure elucidation of novel metabolites or metabolites where no authentic standards are available for comparison. Source


Kirkpatrick G.J.,Strathclyde Institute of Pharmacy and Biomedical science | Plumb J.A.,University of Glasgow | Sutcliffe O.B.,Strathclyde Institute of Pharmacy and Biomedical science | Flint D.J.,Strathclyde Institute of Pharmacy and Biomedical science | Wheate N.J.,Strathclyde Institute of Pharmacy and Biomedical science
Journal of Inorganic Biochemistry | Year: 2011

Aquated cisplatin was added to half-generation PAMAM dendrimers and the resultant complexes were purified by centrifuge. The drug-dendrimer complexes were then characterised by 1-D and diffusion 1H NMR and ICP-AES. The amount of drug bound was found to increase in proportion with dendrimer size: G3.5, 22 cis-{Pt(NH 3) 2} molecules per dendrimer; G4.5, 37; G5.5, 54; and G6.5, 94, which represent only a fraction of the available binding sites on each dendrimer (68, 58, 42 and 37%, respectively). Drug release studies showed that some drug remains bound to the dendrimer even after prolonged incubation with 5′-GMP at temperatures of 60 °C for over a week (percentage of drug released 18, 30, 35 and 63%, respectively). Attachment of the drug was found to decrease the radius of the dendrimers. Finally, the effect of the dendrimer on drug cytotoxicity was determined using in vitro assays with the A2780, A2780cis and A2780cp ovarian cancer cell lines. The free dendrimers display no cytotoxicity whilst the drug-dendrimer complexes showed moderate activity. In vivo activity was examined using an A2780 tumour xenograft. Cisplatin, at its maximum tolerated dose of 6 mg/kg, reduced tumour size by 33% compared to an untreated control group. The G6.5 cisplatin-dendrimer complex was administered at two doses (6 and 8 mg/kg equivalent of cisplatin). Both were well tolerated by the mice. The lower dose displayed comparable activity to cisplatin with a tumour volume reduction of 32%, but the higher dose was significantly more active than free cisplatin with a tumour reduction of 45%. © 2011 Elsevier Inc. All rights reserved. Source


Millar D.I.A.,University of Edinburgh | Marshall W.G.,Rutherford Appleton Laboratory | Oswald I.D.H.,Strathclyde Institute of Pharmacy and Biomedical science | Pulham C.R.,University of Edinburgh
Crystallography Reviews | Year: 2010

This article reviews how the advances in the techniques for the collection and analysis of high-pressure X-ray and neutron diffraction data, augmented by spectroscopic data, now permit the accurate determination of the full crystal structure of energetic materials under extreme conditions. Using these methods, the crystal structure of the high-pressure γ-form of RDX (1,3,5-trinitrohexahydro-s-triazine) has been determined-the first case of a high-pressure structure of an energetic material. In addition, the crystal structure of the highly metastable β-form has been determined and, contrary to the previous reports, has been shown to be different from the form obtained at elevated temperatures and pressures. © 2010 Taylor & Francis. Source


Zhang T.,Strathclyde Institute of Pharmacy and Biomedical science | Watson D.G.,Strathclyde Institute of Pharmacy and Biomedical science
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2016

Although many hydrophilic interaction liquid chromatography-high resolution mass spectrometry (HILIC-HRMS) methods have been developed and applied for untargeted metabolite profiling in clinical metabolomics, according to the literature, the suitability of these HILIC-HRMS methods has not been fully evaluated with respect to their performance when they are subjected to statistical analysis. In this study, using a series of human urine samples we investigated the effect of technical variations on multivariate and univariate analysis of the data collected using a previously developed HILIC-HRMS method for untargeted urinary metabolite profiling in clinical metabolomics. The technical variation introduced by sample preparation was more significant than that produced by the HILIC-HRMS method. By using an orthogonal partial least squares (OPLS) model, subtle fold-changes were accurately measured in the urine samples spiked with 13C and 15N isotope labelled amino acids at different concentrations. The robustness of this HILIC method was also evaluated by analysing the obtained data from a single urine sample following manipulation of several primary LC parameters. High reproducibility in the chromatographic performance of three ZIC-pHILIC columns with different batch numbers indicated the reliability of the polymer based zwitterionic stationary phase allowing column replacement without compromising the performance of the method. © 2016 Elsevier B.V. Source

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