Ian D Wilson

Imperial College London, Londinium, England, United Kingdom

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Publications (380)1279.21 Total impact

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    ABSTRACT: 1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31–44% of human subjects. 4. Metabolite profiling of urine by 1H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.
    Xenobiotica 10/2014; · 1.98 Impact Factor
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    ABSTRACT: The hepatic cytochrome P450 reductase null (HRN) mouse, which has no functional hepatic Cyp P450s, may represent a useful model for examining extra-hepatic P450-related oxidative metabolism. Here the pharmacokinetics and metabolic fate of midazolam, a drug known to undergo such extra-hepatic metabolism, have been investigated in the HRN mouse and compared with a phenotypically normal strain (C57BL/6J). In addition, the effects of co-administration of the pan-P450 inhibitor 1′-aminobenzotriazole (ABT) on the metabolic profile have been compared in both strains. Significant pharmacokinetic differences for midazolam were observed between the two strains of mice with the HRN mice showing lower circulating concentrations of 1′-hydroxymidazolam but higher concentrations of 1′-hydroxymidazolam-O-glucuronide. A significant increase in midazolam exposure was seen upon ABT exposure for both strains of mice, but no differences in the area under the concentration time curves (AUC) for the monitored metabolites were observed. Although oxidative metabolism of midazolam was not abolished, significant decreases in 1′-hydroxymidazolam formation ratios were observed for both strains of mice exposed to ABT. Metabolite profiling of blood and bile showed a number of qualitative and quantitative differences between HRN and normal mice. These differences in midazolam metabolism between the two strains of mice clearly demonstrate the role that liver P450 enzymes play in the murine metabolism of midazolam. The fate of the compound in the HRN mice shows the importance of extrahepatic metabolism and also showed that these mice appear to be more capable of forming circulating phase II glucuronides than the normal strain.
    Biochemical Pharmacology. 10/2014;
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    ABSTRACT: We review the separations currently employed in the field of global metabolic profiling and based on the use of liquid chromatography (LC) coupled to mass spectrometry. Currently, most LC separations are performed using reversed-phase (RP) methods, with hydrophilic interaction chromatography a popular choice for polar compounds that are not well served by the RP mode. The use of ultra-(high)-performance LC [U(H)PLC] is seen to be increasingly replacing conventional high-performance LC (HPLC) in metabonomic/metabolomic applications as its benefits are seen as essential for rapid, high-resolution sample analysis. We discuss alternative, and emerging, methods of sample profiling, based on the miniaturization of HPLC-type separations, or the application of supercritical high-performance and ultra-high-performance chromatographic separation.
    TrAC Trends in Analytical Chemistry 10/2014; · 6.35 Impact Factor
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    ABSTRACT: Many carboxylic-acid-containing drugs cause liver injury in humans. Examples include fenclozic acid, which was withdrawn due to jaundice observed in clinical trials, and diclofenac, which remains widely prescribed despite being associated with liver damage. To explore whether metabolic bioactivation mediated by cytochrome P450 (CYP) or UDP-dependent gluronyltransferase (UGT) enzymes could play a role in these toxicities, covalent binding (CVB) assays were performed using liver microsomal incubations from wild-type and hepatic cytochrome P450 reductase null (HRN™) mice, which are deficient in hepatic CYP activity. Additionally, wild-type and HRN™ mice were administered fenclozic acid and diclofenac orally for 7 days and the effect on clinical chemistry biomarkers and liver pathology investigated. High levels of CYP-mediated CVB of [14C]-fenclozic acid and [14C]-diclofenac were observed in wild-type microsomes, but not in HRN™ microsomes. No UDPGA-mediated CVB was detected in microsomes incubated with [14C]-fenclozic acid. Exposure to fenclozic acid (100 mg/kg) for 7 days resulted in a significant (p < 0.05) increase in plasma alanine amino transferase (ALT) in wild-type but not HRN™ mice. In HRN™ mice liver histopathology changes and markedly elevated ALT, glutamate dehydrogenase and alkaline phosphatase levels were evident. Treatment with diclofenac and fenclozic acid “normalised” the liver clinical chemistry parameters. These data demonstrate that fenclozic acid undergoes CYP but not UGT mediated bioactivation and that HRN™ mice can provide a valuable insight into the role of hepatic CYPs in drug metabolism. However, HRN™ mice are not well suited to investigations of liver toxicity, due to impaired background liver function.
    Toxicology Letters 09/2014; 229(10):S40. · 3.15 Impact Factor
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    ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs on the market. Whilst they are considered safe, several NSAIDs have been withdrawn from the market as a result of adverse drug reactions. NSAIDs are extensively metabolised to their 1-β-O-acyl glucuronides (AGs), and the risk of NSAID AGs covalently modifying biomacromolecules such as proteins or DNA, leading to immune responses and cellular dysfunction constitutes a major concern in drug discovery and development. The assessment of the degree of protein modification and potential toxicity of individual NSAID AGs is therefore of importance in both drug monitoring and development. Herein, we report the covalent reaction of 1-β-O-acyl glucuronides of ibuprofen and several NSAID analogues with human serum albumin (HSA) protein in vitro under concentrations encountered in therapy. Stable transacylation and glycosylation adducts are formed; the observed protein product ratios can be rationalised by the degree of α-substitution in the acyl group. Structure-based protein reactivity correlations of AGs, such as these, may prove a useful tool in distinguishing between carboxylic acid-containing drugs of similar structure that ultimately prove beneficial (e.g., ibuprofen) from those that prove toxic (e.g., ibufenac).
    Chemical Science 07/2014; · 8.31 Impact Factor
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    ABSTRACT: Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3s at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 04/2014; · 2.78 Impact Factor
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    ABSTRACT: Background: Mevalonic acid (MVA), as a product of 3-hydroxy-3-methylglutaryl coenzyme A reductase, represents a potential multipurpose biomarker in health and disease. A translational urinary MVA quantification method was developed, validated and used to demonstrate the diurnal variation of urinary MVA excretion in rats and healthy children. Methods: Urinary MVA was converted to mevalonolactone at pH 2, extracted with ethyl acetate and quantified by reversed-phase liquid chromatography-tandem mass spectrometry. Results: The assay had a dynamic range of 0.0156-10 µg/ml with precision <15% CV, accuracy 85-115% and was transferred between laboratories. Urinary MVA excretion in rats and healthy children displayed a diurnal variation consistent with the known diurnal variation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Conclusion: Urinary MVA can be quantified accurately over a wide dynamic range by a validated translational and transferable method with biomarker capability.
    Bioanalysis 04/2014; 6(7):919-33. · 3.25 Impact Factor
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    ABSTRACT: Hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial-host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared to a control group. Urine samples were collected at day zero, four and eight, and analyzed by HILIC-MS. Multivariate data analysis was applied to the urinary metabolic profiles to identify biochemical variation between the treatment groups. Principal component analysis found a clear distinction between those animals receiving antibiotics and the control animals, with twenty-nine discriminatory compounds of which twenty were down-regulated and nine up-regulated upon treatment. In the treatment group receiving antibiotics for four days, a recovery effect was observed for seven compounds after cessation of antibiotic administration. Thirteen discriminatory compounds could be putatively identified based on their accurate mass, including aconitic acid, benzenediol sulfate, ferulic acid sulfate, hippuric acid, indoxyl sulfate, penicillin G, phenol and vanillin 4-sulfate. The rat urine samples had previously been analyzed by capillary electrophoresis (CE) with MS detection and proton nuclear magnetic resonance ((1)H NMR) spectroscopy. Using CE-MS and (1)H NMR spectroscopy seventeen and twenty-five discriminatory compounds were found, respectively. Both hippuric acid and indoxyl sulfate were detected across all three platforms. Additionally, eight compounds were observed with both HILIC-MS and CE-MS. Overall, HILIC-MS appears to be highly complementary to CE-MS and (1)H NMR spectroscopy, identifying additional compounds that discriminate the urine samples from antibiotic-treated and control rats.
    Journal of pharmaceutical and biomedical analysis 01/2014; 92C:98-104. · 2.45 Impact Factor
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    ABSTRACT: Abstract 1. The biotransformation, hepatic transporter and blood chemistry effects of troglitazone were investigated following 7 days of dosing at 600 mg/kg/day to chimeric murinized or humanized FRG mice, Mo-FRG and Hu-FRG mice, respectively. 2. Clinical chemistry and histopathology analysis revealed a significant drop in humanization over the time course of the study for the Hu-FRG mice but no significant changes associated with troglitazone treatment in either the Mo-FRG or the Hu-FRG models. No changes in transporter expression in livers of these mice were observed. Oxidative and conjugative metabolic pathways were identified with a 15- to 18-fold increase in formation of troglitazone sulfate in the Hu-FRG mice compared with the Mo-FRG mice in blood and bile, respectively. This resembles the troglitazone metabolism in human and these data are comparable with the formation of this metabolite in the chimeric uPA(+/+)/SCID mice. 3. However, larger amounts of troglitazone glucuronide were also observed in the Hu-FRG mouse compared with the Mo-FRG mouse which may be an effect of the drop in humanization of the Hu-FRG mouse during the study. 4. Highly humanized mice have a considerable potential in providing a useful first insight into circulating human metabolites of candidate drugs metabolized in the liver.
    Xenobiotica 01/2014; · 1.98 Impact Factor
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    ABSTRACT: Ultra high resolution SFC-MS (on sub-2 μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3 seconds at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile.
    Journal of Chromatography B. 01/2014;
  • Helen G Gika, Ian D Wilson
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    ABSTRACT: Alcohol-related disorders are multifaceted since ethanol can induce profound metabolic perturbations when taken in excess. Global metabolic profiling strategies may aid the understanding of ethanol-related effects by shedding light on these metabolic changes and potentially revealing unknown mechanisms of ethanol toxicity. Here an overview of studies designed to explore the effects of alcohol (ethanol) consumption using holistic metabolite profiling approaches (metabonomics/metabolomics) is presented, demonstrating the potential of this methodology. The analytical technologies used (NMR, GC-MS and LC-MS), have been applied to the profiling of serum, plasma, urine and tissues, obtained from animal models or humans, after exposure to alcohol. From the metabolic profiling data of a range of biological samples, a number of endogenous metabolites have been proposed as potential ethanol consumption-related biomarkers. The biomarkers suggested by these studies, and the biochemical insights that they provide for understanding the effects of ethanol mechanisms of toxicity, are discussed.
    Bioanalysis 01/2014; 6(1):59-77. · 3.25 Impact Factor
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    ABSTRACT: The effective analysis of polar ionic metabolites by LC–MS, such as those encountered in central carbon metabolism, represents a major problem for metabolic profiling that is not adequately addressed using strategies based on either reversed-phase or HILIC methods. Here we have compared analysis of central carbon metabolites on optimized methods using HILIC, porous graphitic carbon or ion pair chromatography (IPC) using tributyl ammonium as IP reagent. Of the 3 chromatographic approaches examined only IPC enabled us to obtain a robust analytical methodology. This system was used to profile more than a hundred endogenous metabolic intermediates in urine, serum and tissue samples. However, whilst we found IPC to be the best of the approaches examined considerable care was still needed to obtain robust data. Thus, in excess of 40 of representative biological samples were needed to “condition” a new analytical column and further 10 matrix injections were then required at the beginning of each analytical batch in order to obtain robust and reproducible chromatographic separations. An additional limitation that we have found was that, for a small number of phosphorylated and poly carboxylic acid metabolites, measurement was only possible if the analytes were present in relatively high concentrations. We also found that, whilst this methodology could be used for the analysis of both in vitro cell culture media, cell extracts, tissue, and biological fluids (blood, urine), for the best results columns should only be used to analyze a single matrix. However, despite the need for extensive column conditioning, and the manifold disadvantages resulting from the contamination of the separation system and mass spectrometer with the ion pair reagent, IPC-MS currently provides the best means of analyzing these polar, ionic and problematic metabolites.
    Journal of Chromatography A. 01/2014; 1349:60–68.
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    ABSTRACT: The present review aims to critically discuss some of the major problems and limitations of LC-MS based metabolomics as experienced from an analytical chemistry standpoint. Metabolomics offers distinct advantages to a variety of life sciences. Continuous development of the field has been realised due to intensive efforts from a great many scientists from widely divergent backgrounds and research interests as demonstrated by the contents of this special issue. The aim of this commentary is to describe current hindrances to field's progress, (some unique to metabolomics, some common with other omics fields or with conventional targeted bioanalysis) to propose some potential solutions to overcome these constraints and to provide a future perspective for likely developments in the field
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 01/2014; · 2.78 Impact Factor
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    ABSTRACT: Animal models are invaluable tools which allow us to investigate the microbiome-host dialogue. However, experimental design introduces biases in the data that we collect, also potentially leading to biased conclusions. With obesity at pandemic levels animal models of this disease have been developed; we investigated the role of experimental design on one such rodent model. We used 454 pyrosequencing to profile the faecal bacteria of obese (n = 6) and lean (homozygous n = 6; heterozygous n = 6) Zucker rats over a 10 week period, maintained in mixed-genotype cages, to further understand the relationships between the composition of the intestinal bacteria and age, obesity progression, genetic background and cage environment. Phylogenetic and taxon-based univariate and multivariate analyses (non-metric multidimensional scaling, principal component analysis) showed that age was the most significant source of variation in the composition of the faecal microbiota. Second to this, cage environment was found to clearly impact the composition of the faecal microbiota, with samples from animals from within the same cage showing high community structure concordance, but large differences seen between cages. Importantly, the genetically induced obese phenotype was not found to impact the faecal bacterial profiles. These findings demonstrate that the age and local environmental cage variables were driving the composition of the faecal bacteria and were more deterministically important than the host genotype. These findings have major implications for understanding the significance of functional metagenomic data in experimental studies and beg the question; what is being measured in animal experiments in which different strains are housed separately, nature or nurture?
    PLoS ONE 01/2014; 9(9):e100916. · 3.53 Impact Factor
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    Kristin Samuelsson, Ian D Wilson
    Xenobiotica 01/2014; 44(2):95. · 1.98 Impact Factor
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    ABSTRACT: Abstract 1. Metabonomic analysis, via a combination of untargeted and targeted liquid chromatography-mass spectrometry (LC-MS) and untargeted (1)H NMR spectroscopy-based metabolite profiling, was performed on aqueous (AQ) and organic liver extracts from control (SCID) and chimeric humanized (PXB) mice dosed with troglitazone at 0, 300 and 600 mg/kg/day for seven days. 2. LC-MS analysis of AQ liver extracts showed a more "human-like" profile for troglitazone metabolites for PXB, compared with SCID, mice. 3. LC-MS detected differences in endogenous metabolites, particularly lipid species in dosed mice, including elevated triacylglycerols and 1-alkyl,2-acylglycerophosphates as well as lowered diacylglycerophosphocholines and 1-alkyl,2-acylglycerophosphocholines for PXB compared with SCID mouse liver extracts. Following drug administration changes in the relative proportions of the ions for various unsaturated fatty acids were observed for both types of mouse, some of which were specific to PXB or SCID mice. 4. (1)H NMR spectroscopy revealed that AQ PXB mouse liver extracts had elevated amounts of inosine, fumarate, creatine, aspartate, trimethylamine N-oxide, glycerophosphocholine, phosphocholine, choline, glutamine, glutamate, acetate, alanine and lactate relative to SCID mice and decreased histidine, glycogen, α- and β-glucose, taurine, and glutathione. Increased uracil and tyrosine concentrations were detected for PXB mice on troglitazone administration. 5. Metabonomic profiling thus showed clear differences between humanized and SCID mice, including after administration of troglitazone.
    Xenobiotica 12/2013; · 1.98 Impact Factor
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    ABSTRACT: Abstract 1. The distribution, metabolism, excretion and hepatic effects of fenclozic acid were investigated following a single oral dose of 10 mg/kg to hepatic reductase null (HRN) mice. 2. The majority of the [(14)C]-fenclozic acid was eliminated via the urine/aqueous cage wash, (55 %) with a smaller portion excreted in the faeces, (5 %). The total recovery of radioactivity in the excreta over the 72 h period studied was ca. 60%. 3. Metabolism of fenclozic acid in the HRN mice was entirely to the carboxylic acid function and was dominated by amino acid conjugation to glycine and taurine, with lesser amounts of an acyl glucuronide. 4. Whole body autoradiography of mice showed general distribution into all tissues except the brain. Radioactivity was still detectable in the kidney and liver of the HRN mice at 72 h post-dose. Covalent binding studies showed evidence of binding to kidney, liver and plasma proteins however, the degree of binding was less than 50 pmol equiv/mg protein for all tissues. 5. The HRN mouse appears to be a useful in vivo model for the study of the Phase II conjugation metabolism of fenclozic acid in the absence of hepatic cytochrome P450-related oxidative metabolism.
    Xenobiotica 12/2013; · 1.98 Impact Factor
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    ABSTRACT: Metabonomic studies use complex biological samples (blood plasma/serum, tissues, etc.) that when analysed with high-performance liquid chromatography/mass spectrometry (HPLC/MS) or nuclear magnetic resonance (NMR) generate profiles that may contain many thousands of features. These profiles can be difficult to interpret with the majority of the features contributing little to the study. As such there is an argument for the development of techniques that can simplify the problem by targeting particular classes of compounds. In this study ultra-performance liquid chromatography/inductively coupled plasma mass spectrometry (UPLC/ICP-MS) was used to profile tumour tissue and plasma samples for phosphorus- and sulfur-containing metabolites. These samples were xenograft tumours (derived from breast, lung and colon cell lines) and plasma obtained from nude mice. Plasma was also obtained from non-tumour-bearing mice as a control. Due to isobaric interferences this method took advantage of the dynamic reaction cell within the ICP-MS system to react the phosphorus and sulfur ions with oxygen. The PO(+) and SO(+) ions were then monitored free of interferences. The total phosphorus and sulfur within each sample was also recorded using flow injection ICP-MS. A robust quality control system based on pooled sample replicate analysis was used throughout the study. Determination of the total phosphorus and sulfur content of each sample was sufficient in itself for statistical differentiation between the majority of the cell lines analysed. Subsequent reversed-phase chromatographic profiling of the organic tumour and plasma extracts revealed the presence of a number of well-retained phosphorus-containing compounds that showed tumour-specific profiles. Reversed-phase profiling was not suitable for the sulfur-containing compounds which eluted with the solvent front. This study has shown the potential use of UPLC/ICP-MS to differentiate between tumour cell lines, using both plasma and tumour tissue samples, based solely on metabolites that contain phosphorus or sulfur. Whilst further work is required to identify these compounds this methodology shows the ability of the described methods to provide targets for future biomarker discovery studies. Copyright © 2013 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 11/2013; 27(22):2539-2545. · 2.51 Impact Factor
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    ABSTRACT: Biliary metabolites present at 6 h post-dose following a single oral dose of [14C]-diclofenac (10 mg kg−1) to male bile duct-cannulated C57BL/6 J mice were profiled and identified. Over the 6 h duration of the study ~19.5 % of the administered radioactivity was excreted into the bile as either [14C]-diclofenac or metabolites. When profiled using HPLC with online radiodetection, the presence of at least 13 radiolabelled components was indicated. These compounds were shown, by consecutive reaction mass spectrometry, to comprise a range of hydroxylated metabolites conjugated to either taurine, glucose and/or glucuronic acid. Both phenolic and acylglucuronide-containing metabolites were observed. The confirmation of the presence of these glucuronide conjugates in mouse bile may have important consequences in the light of emerging theories concerning the role of bacterial glucuronidases for the GI-tract toxicity of NSAIDs such as diclofenac.
    Chromatographia 11/2013; · 1.44 Impact Factor
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    ABSTRACT: Based on publication and citation numbers liquid chromatography (LC-MS) has become the major analytical technology in the field of global metabolite profiling. This dominance reflects significant investments from both the research community and instrument manufacturers. Here an overview of the approaches taken for LC-MS-based metabolomics research is given, describing critical steps in the realisation of such studies: study design and its needs, specific technological problems to be addressed and major obstacles in data treatment and biomarker identification. The current state of the art for LC-MS-based analysis in metabonomics/metabolomics is described including recent developments in liquid chromatography, mass spectrometry and data treatment as these are applied in metabolomics underlining the challenges, limitations and prospects for metabolomics research. Examples of the application of metabolite profiling in the life sciences focusing on disease biomarker discovery are highlighted. In addition, new developments and future prospects are described.
    Journal of pharmaceutical and biomedical analysis 07/2013; · 2.45 Impact Factor

Publication Stats

7k Citations
1,279.21 Total Impact Points

Institutions

  • 1999–2014
    • Imperial College London
      • • Department of Surgery and Cancer
      • • Section of Computational and Systems Medicine (CSM)
      • • Faculty of Medicine
      Londinium, England, United Kingdom
  • 2010–2013
    • Universiteit Utrecht
      • • Department of Pharmaceutical Sciences
      • • Division of Biomedical Analysis
      Utrecht, Provincie Utrecht, Netherlands
  • 2007–2013
    • Aristotle University of Thessaloniki
      • • Department of Chemical Engineering
      • • School of Chemistry
      • • Laboratory of Analytical Chemistry
      Thessaloníki, Kentriki Makedonia, Greece
    • The University of Manchester
      • • Manchester Interdisciplinary Biocentre (MIB)
      • • Manchester Centre for Integrative Systems Biology (MCISB)
      • • Manchester Medical School
      Manchester, ENG, United Kingdom
    • Huntingdon Life Sciences
      Huntingdon, England, United Kingdom
    • Arizona State University
      Phoenix, Arizona, United States
  • 2006–2013
    • University of Liverpool
      • Department of Chemistry
      Liverpool, England, United Kingdom
    • Nottingham Trent University
      Nottigham, England, United Kingdom
  • 2003–2013
    • Loughborough University
      • Department of Chemistry
      Loughborough, ENG, United Kingdom
  • 1978–2013
    • Keele University
      • • School of Physical and Geographical Sciences
      • • Department of Chemistry
      Newcastle-under-Lyme, England, United Kingdom
  • 2000–2012
    • AstraZeneca
      • Drug Metabolism & Pharmacokinetics (DMPK)
      Tukholma, Stockholm, Sweden
  • 2011
    • King's College London
      • Department of Pharmacy
      London, ENG, United Kingdom
  • 2008–2010
    • University of Leicester
      • Department of Cancer Studies and Molecular Medicine
      Leicester, ENG, United Kingdom
  • 2006–2007
    • Waters Corporation
      Milford, Massachusetts, United Kingdom
  • 1999–2003
    • University of Tuebingen
      • Institute of Inorganic Chemistry
      Tübingen, Baden-Wuerttemberg, Germany
  • 1992–2002
    • University of London
      Londinium, England, United Kingdom
  • 1988–2000
    • Birkbeck, University of London
      Londinium, England, United Kingdom