Metabolomics in clinical and forensic toxicology, sports anti-doping and veterinary residues.
Abstract: Metabolomics is a multidisciplinary field providing workflows for complementary approaches to conventional analytical determinations. It allows for the study of metabolically related groups of compounds or even the study of novel pathways within the biological system. The procedural stages of metabolomics; experimental design, sample preparation, analytical determinations, data processing and statistical analysis, compound identification and validation strategies are explored in this review. The selected approach will depend on the type of study being conducted. Experimental design influences the whole metabolomics workflow and thus needs to be properly assessed to ensure sufficient sample size, minimal introduced and biological variation and appropriate statistical power. Sample preparation needs to be simple, yet potentially global in order to detect as many compounds as possible. Analytical determinations need to be optimised either for the list of targeted compounds or a universal approach. Data processing and statistical analysis approaches vary widely and need to be better harmonised for review and interpretation. This includes validation strategies that are currently deficient in many presented workflows. Common compound identification approaches have been explored in this review. Metabolomics applications are discussed for clinical and forensic toxicology, human and equine sports anti-doping and veterinary residues.
© 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
Publication Date: 2022-03-08 PubMed ID: 35194967PubMed Central: PMC9544538DOI: 10.1002/dta.3245Google Scholar: Lookup
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Summary
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The research paper provides an in-depth examination of the procedural stages in metabolomics, which is a multidisciplinary field used as a supplementary approach to customary analytical findings. It identifies the potential application of metabolomics in areas like clinical and forensic toxicology, sports anti-doping, and veterinary residues.
Metabolomics: An Overview
- Metabolomics is a multidisciplinary field that involves the detailed study of metabolic groups or compounds, and the identification of new pathways within biological systems. It works as a complementary methodology to routine analytical determinations.
Procedural Stages in Metabolomics
- The research paper delves into various procedural stages of metabolomics which include experimental design, sample preparation, analytical determinations, data processing and statistical analysis, compound identification and validation strategies.
- The choice of procedure hugely depends on the type of study being conducted.
Experimental Design
- A well-thought-out experimental design impacts the whole metabolomics workflow. It should consider factors such as ensuring a sufficient sample size, minimizing introduced and biological variation, and achieving acceptable statistical power.
Sample Preparation
- The sample preparation in metabolomics needs to be straightforward while trying to detect as many compounds as possible, which means it needs to be potentially global.
Analytical Determinations
- These need optimization either for the list of targeted compounds or for a more generalized approach. The methods vary widely across studies.
Data Processing and Statistical Analysis
- Approaches for data processing and statistical analysis often differ widely and need harmonization for easier review and interpretation.
Validation Strategies
- These are typically poor in most presented workflows, indicating a significant gap which needs addressing.
Compound Identification
- The paper explores different approaches to compound identification used in metabolomics.
Applications of Metabolomics
- The paper gives an overview of the potential application of metabolomics in several sectors such as clinical and forensic toxicology, human and equine sports anti-doping, and the identification of veterinary residues.
Cite This Article
APA
Keen B, Cawley A, Reedy B, Fu S.
(2022).
Metabolomics in clinical and forensic toxicology, sports anti-doping and veterinary residues.
Drug Test Anal, 14(5), 794-807.
https://doi.org/10.1002/dta.3245 Publication
Researcher Affiliations
- Centre for Forensic Science, University of Technology Sydney, Broadway, New South Wales, Australia.
- Australian Racing Forensic Laboratory, Racing NSW, Sydney, New South Wales, Australia.
- School of Mathematical and Physical Sciences, University of Technology Sydney, Broadway, New South Wales, Australia.
- Centre for Forensic Science, University of Technology Sydney, Broadway, New South Wales, Australia.
MeSH Terms
- Animals
- Doping in Sports
- Forensic Toxicology
- Horses
- Metabolomics
- Sports
- Workflow
References
This article includes 153 references
- Lindon JC, Holmes E, Nicholson JK. So what's the deal with metabonomics?. Anal Chem 2003 Sep 1;75(17):384A-391A.
- Holmes E, Antti H. Chemometric contributions to the evolution of metabonomics: mathematical solutions to characterising and interpreting complex biological NMR spectra.. Analyst 2002 Dec;127(12):1549-57.
- Kenney B, Shockor JP. Complementary NMR and LC‐MS technologies for Metabonomic Studies. PharmaGenomics 2003;3(9):56.
- Nicholson JK, Wilson ID. Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism.. Nat Rev Drug Discov 2003 Aug;2(8):668-76.
- Nobeli I, Thornton JM. A bioinformatician's view of the metabolome.. Bioessays 2006 May;28(5):534-45.
- Rochfort S. Metabolomics reviewed: a new "omics" platform technology for systems biology and implications for natural products research.. J Nat Prod 2005 Dec;68(12):1813-20.
- Patti GJ, Yanes O, Siuzdak G. Innovation: Metabolomics: the apogee of the omics trilogy.. Nat Rev Mol Cell Biol 2012 Mar 22;13(4):263-9.
- Casadei L, Valerio M, Manetti C. Metabolomics: Challenges and Opportunities in Systems Biology Studies.. Methods Mol Biol 2018;1702:327-336.
- Rico E, González O, Blanco ME, Alonso RM. Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS.. Anal Bioanal Chem 2014 Nov;406(29):7641-52.
- Dettmer K, Aronov PA, Hammock BD. Mass spectrometry-based metabolomics.. Mass Spectrom Rev 2007 Jan-Feb;26(1):51-78.
- Courant F, Antignac JP, Dervilly-Pinel G, Le Bizec B. Basics of mass spectrometry based metabolomics.. Proteomics 2014 Nov;14(21-22):2369-88.
- Klein DJ, Anthony TG, McKeever KH. Metabolomics in equine sport and exercise.. J Anim Physiol Anim Nutr (Berl) 2021 Jan;105(1):140-148.
- Di Girolamo F, Lante I, Muraca M, Putignani L. The Role of Mass Spectrometry in the "Omics" Era.. Curr Org Chem 2013 Dec;17(23):2891-2905.
- Teale P, Barton C, Driver PM, Kay RG. Biomarkers: unrealized potential in sports doping analysis.. Bioanalysis 2009 Sep;1(6):1103-18.
- Mooney MH, Elliott CT, Le Bizec B. Combining biomarker screening and mass‐spectrometric analysis to detect hormone abuse in cattle. TrAC 2009;28(6):665‐675.
- Tohge T, Fernie AR. Web-based resources for mass-spectrometry-based metabolomics: a user's guide.. Phytochemistry 2009 Mar;70(4):450-6.
- Kaddurah-Daouk R, Kristal BS, Weinshilboum RM. Metabolomics: a global biochemical approach to drug response and disease.. Annu Rev Pharmacol Toxicol 2008;48:653-83.
- Lenz EM, Wilson ID. Analytical strategies in metabonomics.. J Proteome Res 2007 Feb;6(2):443-58.
- Cajka T, Fiehn O. Toward Merging Untargeted and Targeted Methods in Mass Spectrometry-Based Metabolomics and Lipidomics.. Anal Chem 2016 Jan 5;88(1):524-45.
- Fragkaki AG, Kioukia-Fougia N, Kiousi P, Kioussi M, Tsivou M. Challenges in detecting substances for equine anti-doping.. Drug Test Anal 2017 Sep;9(9):1291-1303.
- Narduzzi L, Dervilly G, Audran M, Le Bizec B, Buisson C. A role for metabolomics in the antidoping toolbox?. Drug Test Anal 2020 Jun;12(6):677-690.
- Hendriks MM, van Eeuwijk FA, Jellema RH. Data‐processing strategies for metabolomics studies. TrAC 2011;30(10):1685‐1698.
- van den Berg RA, Hoefsloot HC, Westerhuis JA, Smilde AK, van der Werf MJ. Centering, scaling, and transformations: improving the biological information content of metabolomics data.. BMC Genomics 2006 Jun 8;7:142.
- Wanichthanarak K, Jeamsripong S, Pornputtapong N, Khoomrung S. Accounting for biological variation with linear mixed-effects modelling improves the quality of clinical metabolomics data.. Comput Struct Biotechnol J 2019;17:611-618.
- Narduzzi L, Buisson C, Morvan ML, Marchand A, Audran M, Le Bouc Y, Varlet-Marie E, Ericsson M, Le Bizec B, Dervilly G. Coupling Complete Blood Count and Steroidomics to Track Low Doses Administration of Recombinant Growth Hormone: An Anti-Doping Perspective.. Front Mol Biosci 2021;8:683675.
- Petersen AK, Krumsiek J, Wägele B, Theis FJ, Wichmann HE, Gieger C, Suhre K. On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies.. BMC Bioinformatics 2012 Jun 6;13:120.
- Scalbert A, Brennan L, Fiehn O, Hankemeier T, Kristal BS, van Ommen B, Pujos-Guillot E, Verheij E, Wishart D, Wopereis S. Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research.. Metabolomics 2009 Dec;5(4):435-458.
- Baduel C, Mueller JF, Tsai H, Gomez Ramos MJ. Development of sample extraction and clean-up strategies for target and non-target analysis of environmental contaminants in biological matrices.. J Chromatogr A 2015 Dec 24;1426:33-47.
- Houghton E, Maynard S. Some aspects of doping and medication control in equine sports.. Handb Exp Pharmacol 2010;(195):369-409.
- Duluard A, Bailly‐Chouriberry L, Kieken F, Popot MA, Bonnaire Y. Longitudinal follow‐up on racehorses: Veterinary and analytical issues. A one‐year study of French trotters. 18th Int Conf Racing Anal Vets 2010;27‐34.
- Cui L, Lu H, Lee YH. Challenges and emergent solutions for LC-MS/MS based untargeted metabolomics in diseases.. Mass Spectrom Rev 2018 Nov;37(6):772-792.
- Eisenhofer G, Lenders JW, Siegert G, Bornstein SR, Friberg P, Milosevic D, Mannelli M, Linehan WM, Adams K, Timmers HJ, Pacak K. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status.. Eur J Cancer 2012 Jul;48(11):1739-49.
- Ibáñez M, Sancho JV, Bijlsma L, van Nuijs ALN, Covaci A, Hernández F. Comprehensive analytical strategies based on high‐resolution time‐of‐flight mass spectrometry to identify new psychoactive substances. TrAC 2014;57:107‐117.
- van de Merbel NC, Hendriks G, Imbos R, Tuunainen J, Rouru J, Nikkanen H. Quantitative determination of free and total dopamine in human plasma by LC-MS/MS: the importance of sample preparation.. Bioanalysis 2011 Sep;3(17):1949-61.
- Bylda C, Thiele R, Kobold U, Volmer DA. Recent advances in sample preparation techniques to overcome difficulties encountered during quantitative analysis of small molecules from biofluids using LC-MS/MS.. Analyst 2014 May 21;139(10):2265-76.
- Lu X, Zhao X, Bai C, Zhao C, Lu G, Xu G. LC-MS-based metabonomics analysis.. J Chromatogr B Analyt Technol Biomed Life Sci 2008 Apr 15;866(1-2):64-76.
- Tulipani S, Llorach R, Urpi-Sarda M, Andres-Lacueva C. Comparative analysis of sample preparation methods to handle the complexity of the blood fluid metabolome: when less is more.. Anal Chem 2013 Jan 2;85(1):341-8.
- Michopoulos F, Theodoridis G, Smith CJ, Wilson ID. Metabolite profiles from dried biofluid spots for metabonomic studies using UPLC combined with oaToF-MS.. J Proteome Res 2010 Jun 4;9(6):3328-34.
- Zhao L, Lucas D, Long D, Richter B, Stevens J. Multi-class multi-residue analysis of veterinary drugs in meat using enhanced matrix removal lipid cleanup and liquid chromatography-tandem mass spectrometry.. J Chromatogr A 2018 May 11;1549:14-24.
- Contrepois K, Jiang L, Snyder M. Optimized Analytical Procedures for the Untargeted Metabolomic Profiling of Human Urine and Plasma by Combining Hydrophilic Interaction (HILIC) and Reverse-Phase Liquid Chromatography (RPLC)-Mass Spectrometry.. Mol Cell Proteomics 2015 Jun;14(6):1684-95.
- Davis MT, Auger P, Spahr C, Patterson SD. Cancer biomarker discovery via low molecular weight serum proteome profiling - Where is the tumor?. Proteomics Clin Appl 2007 Dec;1(12):1545-58.
- Van Eeckhaut A, Lanckmans K, Sarre S, Smolders I, Michotte Y. Validation of bioanalytical LC-MS/MS assays: evaluation of matrix effects.. J Chromatogr B Analyt Technol Biomed Life Sci 2009 Aug 1;877(23):2198-207.
- Zahra PW, Simpson NJK. Application of alternative SPE sorbents and formats for extraction of urine and plasma. 20th Int Conf Racing Anal Vets 2014;20:324‐330.
- Stojiljkovic N, Paris A, Garcia P, Popot MA, Bonnaire Y, Tabet JC, Junot C. Evaluation of horse urine sample preparation methods for metabolomics using LC coupled to HRMS.. Bioanalysis 2014 Mar;6(6):785-803.
- Gonçalves D, Alves G, Soares-da-Silva P, Falcão A. Bioanalytical chromatographic methods for the determination of catechol-O-methyltransferase inhibitors in rodents and human samples: a review.. Anal Chim Acta 2012 Jan 13;710:17-32.
- Madji Hounoum B, Blasco H, Nadal-Desbarats L, Diémé B, Montigny F, Andres CR, Emond P, Mavel S. Analytical methodology for metabolomics study of adherent mammalian cells using NMR, GC-MS and LC-HRMS.. Anal Bioanal Chem 2015 Nov;407(29):8861-72.
- Want EJ, O'Maille G, Smith CA, Brandon TR, Uritboonthai W, Qin C, Trauger SA, Siuzdak G. Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry.. Anal Chem 2006 Feb 1;78(3):743-52.
- Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS.. Anal Chem 2003 Jul 1;75(13):3019-30.
- Bicker J, Fortuna A, Alves G, Falcão A. Liquid chromatographic methods for the quantification of catecholamines and their metabolites in several biological samples--a review.. Anal Chim Acta 2013 Mar 20;768:12-34.
- Poole C. Milestones in the development of liquid‐phase extraction techniques. In: Liquid‐Phase Extraction. Amsterdam, Netherlands: Elsevier; 2020:798.
- Hyde AM, Zultanski SL, Waldman JH, Zhong Y‐L, Shevlin M, Peng F. General principles and strategies for salting‐out informed by the hofmeister series. Org Process Res Dev 2017;21(9):1355‐1370.
- Santana‐Mayor Á, Socas‐Rodríguez B, Herrera‐Herrera AV, Rodríguez‐Delgado MÁ. Current trends in QuEChERS method. A versatile procedure for food, environmental and biological analysis. TrAC Trends Anal Chem 2019;116:214‐235.
- González‐Curbelo MÁ, Socas‐Rodríguez B, Herrera‐Herrera AV, González‐Sálamo J, Hernández‐Borges J, Rodríguez‐Delgado MÁ. Evolution and applications of the QuEChERS method. TrAC Trends Anal Chem 2015;71:169‐185.
- Müller RK. History of doping and doping control. In: Doping in Sports: Biochemical Principles, Effects and Analysis. Berlin, Heidelberg: Springer; 2010:1‐23.
- Allen DR, McWhinney BC. Quadrupole Time-of-Flight Mass Spectrometry: A Paradigm Shift in Toxicology Screening Applications.. Clin Biochem Rev 2019 Aug;40(3):135-146.
- Amirav A, Keshet U, Danon A. Soft Cold EI - approaching molecular ion only with electron ionization.. Rapid Commun Mass Spectrom 2015 Nov 15;29(21):1954-60.
- Pasikanti KK, Ho PC, Chan EC. Development and validation of a gas chromatography/mass spectrometry metabonomic platform for the global profiling of urinary metabolites.. Rapid Commun Mass Spectrom 2008 Oct;22(19):2984-92.
- de Koster CG, Schoenmakers PJ. Chapter 3.1—history of liquid chromatography—mass spectrometry couplings. In: Tranchida PQ, Mondello L, eds. Hyphenations of Capillary Chromatography with Mass Spectrometry. Elsevier; 2020:279‐295.
- Tiller PR, Yu S, Castro-Perez J, Fillgrove KL, Baillie TA. High-throughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time-of-flight system as a 'first-line' approach for metabolite identification studies.. Rapid Commun Mass Spectrom 2008 Apr;22(7):1053-61.
- Rojo D, Barbas C, Rupérez FJ. LC-MS metabolomics of polar compounds.. Bioanalysis 2012 Jun;4(10):1235-43.
- Ruta J, Rudaz S, McCalley DV, Veuthey JL, Guillarme D. A systematic investigation of the effect of sample diluent on peak shape in hydrophilic interaction liquid chromatography.. J Chromatogr A 2010 Dec 24;1217(52):8230-40.
- Kouassi Nzoughet JJ, Dervilly‐Pinel G, Chéreau S. First insights into serum metabolomics of trenbolone/estradiol implanted bovines; screening model to predict hormone‐treated and control animals' status. Metabolomics 2015;11(5):1184‐1196.
- Boulard L, Dierkes G, Ternes T. Utilization of large volume zwitterionic hydrophilic interaction liquid chromatography for the analysis of polar pharmaceuticals in aqueous environmental samples: Benefits and limitations.. J Chromatogr A 2018 Feb 2;1535:27-43.
- Narduzzi L, Royer AL, Bichon E, Guitton Y, Buisson C, Le Bizec B, Dervilly-Pinel G. Ammonium Fluoride as Suitable Additive for HILIC-Based LC-HRMS Metabolomics.. Metabolites 2019 Nov 27;9(12).
- Olsen BA, Pack BW. Hydrophilic Interaction Chromatography a Guide For Practitioners. Hoboken, N.J: John Wiley & Sons, Inc.; 2013.
- Saha S, Walia S, Sharma K, Banerjee K. Suitability of stationary phase for LC analysis of biomolecules.. Crit Rev Food Sci Nutr 2020;60(17):2856-2873.
- Wu Y, Li L. Sample normalization methods in quantitative metabolomics.. J Chromatogr A 2016 Jan 22;1430:80-95.
- Smith CA, Want EJ, O'Maille G, Abagyan R, Siuzdak G. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification.. Anal Chem 2006 Feb 1;78(3):779-87.
- Ghasemi A, Zahediasl S. Normality tests for statistical analysis: a guide for non-statisticians.. Int J Endocrinol Metab 2012 Spring;10(2):486-9.
- Saccenti E, Hoefsloot HC, Smilde AK, Westerhuis JA, Hendriks MM. Reflections on univariate and multivariate analysis of metabolomics data. Metabolomics 2014;10(3):361‐374.
- Ren S, Hinzman A, Kang E, Szczesniak R, Lu L. Computational and statistical analysis of metabolomics data. Metabolomics 2015;11.
- Caesar LK, Kvalheim OM, Cech NB. Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics.. Anal Chim Acta 2018 Aug 27;1021:69-77.
- Heinemann J, Mazurie A, Tokmina‐lukaszewska M, Beilman GJ, Bothner B. Application of support vector machines to metabolomics experiments with limited replicates. Metabolomics 2014;10(6):1121‐1128.
- Marco-Ramell A, Palau-Rodriguez M, Alay A, Tulipani S, Urpi-Sarda M, Sanchez-Pla A, Andres-Lacueva C. Evaluation and comparison of bioinformatic tools for the enrichment analysis of metabolomics data.. BMC Bioinformatics 2018 Jan 2;19(1):1.
- Ortmayr K, Charwat V, Kasper C, Hann S, Koellensperger G. Uncertainty budgeting in fold change determination and implications for non-targeted metabolomics studies in model systems.. Analyst 2016 Dec 19;142(1):80-90.
- Gertsman I, Barshop BA. Promises and pitfalls of untargeted metabolomics.. J Inherit Metab Dis 2018 May;41(3):355-366.
- Hao L, Wang J, Page D, Asthana S, Zetterberg H, Carlsson C, Okonkwo OC, Li L. Comparative Evaluation of MS-based Metabolomics Software and Its Application to Preclinical Alzheimer's Disease.. Sci Rep 2018 Jun 18;8(1):9291.
- Schymanski EL, Jeon J, Gulde R, Fenner K, Ruff M, Singer HP, Hollender J. Identifying small molecules via high resolution mass spectrometry: communicating confidence.. Environ Sci Technol 2014 Feb 18;48(4):2097-8.
- Ruttkies C, Neumann S, Posch S. Improving MetFrag with statistical learning of fragment annotations.. BMC Bioinformatics 2019 Jul 5;20(1):376.
- Tsugawa H, Cajka T, Kind T, Ma Y, Higgins B, Ikeda K, Kanazawa M, VanderGheynst J, Fiehn O, Arita M. MS-DIAL: data-independent MS/MS deconvolution for comprehensive metabolome analysis.. Nat Methods 2015 Jun;12(6):523-6.
- Domingo-Almenara X, Montenegro-Burke JR, Ivanisevic J, Thomas A, Sidibé J, Teav T, Guijas C, Aisporna AE, Rinehart D, Hoang L, Nordström A, Gómez-Romero M, Whiley L, Lewis MR, Nicholson JK, Benton HP, Siuzdak G. XCMS-MRM and METLIN-MRM: a cloud library and public resource for targeted analysis of small molecules.. Nat Methods 2018 Sep;15(9):681-684.
- Lindon JC, Nicholson JK, Holmes E, Keun HC, Craig A, Pearce JT, Bruce SJ, Hardy N, Sansone SA, Antti H, Jonsson P, Daykin C, Navarange M, Beger RD, Verheij ER, Amberg A, Baunsgaard D, Cantor GH, Lehman-McKeeman L, Earll M, Wold S, Johansson E, Haselden JN, Kramer K, Thomas C, Lindberg J, Schuppe-Koistinen I, Wilson ID, Reily MD, Robertson DG, Senn H, Krotzky A, Kochhar S, Powell J, van der Ouderaa F, Plumb R, Schaefer H, Spraul M. Summary recommendations for standardization and reporting of metabolic analyses.. Nat Biotechnol 2005 Jul;23(7):833-8.
- Goodacre R, Broadhurst D, Smilde A. Proposed minimum reporting standards for data analysis in metabolomics. Metabolomics 2007;3(3):231‐241.
- Foubister V. Metabolomics reporting standards proposed. J Proteome Res 2005;4(5):1483.
- Fiehn O, Robertson D, Griffin J. The metabolomics standards initiative (MSI). Metabolomics 2007;3(3):175‐178.
- Dunn WB, Broadhurst DI, Edison A. Quality assurance and quality control processes: summary of a metabolomics community questionnaire. Metabolomics 2017;13(5):1.
- Beger RD, Dunn WB, Bandukwala A, Bethan B, Broadhurst D, Clish CB, Dasari S, Derr L, Evans A, Fischer S, Flynn T, Hartung T, Herrington D, Higashi R, Hsu PC, Jones C, Kachman M, Karuso H, Kruppa G, Lippa K, Maruvada P, Mosley J, Ntai I, O'Donovan C, Playdon M, Raftery D, Shaughnessy D, Souza A, Spaeder T, Spalholz B, Tayyari F, Ubhi B, Verma M, Walk T, Wilson I, Witkin K, Bearden DW, Zanetti KA. Towards quality assurance and quality control in untargeted metabolomics studies.. Metabolomics 2019 Jan 3;15(1):4.
- Beger RD. Interest is high in improving quality control for clinical metabolomics: setting the path forward for community harmonization of quality control standards.. Metabolomics 2018 Dec 18;15(1):1.
- A J, Trygg J, Gullberg J, Johansson AI, Jonsson P, Antti H, Marklund SL, Moritz T. Extraction and GC/MS analysis of the human blood plasma metabolome.. Anal Chem 2005 Dec 15;77(24):8086-94.
- Jonsson P, Gullberg J, Nordström A, Kusano M, Kowalczyk M, Sjöström M, Moritz T. A strategy for identifying differences in large series of metabolomic samples analyzed by GC/MS.. Anal Chem 2004 Mar 15;76(6):1738-45.
- Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA, Fan TW, Fiehn O, Goodacre R, Griffin JL, Hankemeier T, Hardy N, Harnly J, Higashi R, Kopka J, Lane AN, Lindon JC, Marriott P, Nicholls AW, Reily MD, Thaden JJ, Viant MR. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI).. Metabolomics 2007 Sep;3(3):211-221.
- Considine EC, Thomas G, Boulesteix AL, Khashan AS, Kenny LC. Critical review of reporting of the data analysis step in metabolomics.. Metabolomics 2017 Dec 1;14(1):7.
- Broadhurst D, Goodacre R, Reinke SN, Kuligowski J, Wilson ID, Lewis MR, Dunn WB. Guidelines and considerations for the use of system suitability and quality control samples in mass spectrometry assays applied in untargeted clinical metabolomic studies.. Metabolomics 2018;14(6):72.
- Broadhurst DI, Kell DB. Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2006;2(4):171‐196.
- Eriksson L, Trygg J, Wold S. CV‐ANOVA for significance testing of PLS and OPLS® models. J Chemometr 2008;22(11–12):594‐600.
- Gromski PS, Xu Y, Hollywood KA, Turner ML, Goodacre R. The influence of scaling metabolomics data on model classification accuracy. Metabolomics 2014;11(3):684‐695.
- Bahado-Singh RO, Syngelaki A, Akolekar R, Mandal R, Bjondahl TC, Han B, Dong E, Bauer S, Alpay-Savasan Z, Graham S, Turkoglu O, Wishart DS, Nicolaides KH. Validation of metabolomic models for prediction of early-onset preeclampsia.. Am J Obstet Gynecol 2015 Oct;213(4):530.e1-530.e10.
- Guan W, Zhou M, Hampton CY, Benigno BB, Walker LD, Gray A, McDonald JF, Fernández FM. Ovarian cancer detection from metabolomic liquid chromatography/mass spectrometry data by support vector machines.. BMC Bioinformatics 2009 Aug 22;10:259.
- Doué M, Dervilly-Pinel G, Cesbron N, Stefani A, Moro L, Biancotto G, Le Bizec B. Clinical biochemical and hormonal profiling in plasma: a promising strategy to predict growth hormone abuse in cattle.. Anal Bioanal Chem 2015 Jun;407(15):4343-9.
- Yi L, Dong N, Shi S. Metabolomic identification of novel biomarkers of nasopharyngeal carcinoma. RSC Adv 2014;4(13):5994‐5911.
- Rubingh CM, Bijlsma S, Derks EP, Bobeldijk I, Verheij ER, Kochhar S, Smilde AK. Assessing the performance of statistical validation tools for megavariate metabolomics data.. Metabolomics 2006;2(2):53-61.
- Wishart DS. Emerging applications of metabolomics in drug discovery and precision medicine.. Nat Rev Drug Discov 2016 Jul;15(7):473-84.
- Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmüller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R. Metabolomics enables precision medicine: "A White Paper, Community Perspective".. Metabolomics 2016;12(10):149.
- Monni G, Atzori L, Corda V, Dessolis F, Iuculano A, Hurt KJ, Murgia F. Metabolomics in Prenatal Medicine: A Review.. Front Med (Lausanne) 2021;8:645118.
- Yan J, Kuzhiumparambil U, Bandodkar S, Dale RC, Fu S. Cerebrospinal fluid metabolomics: detection of neuroinflammation in human central nervous system disease.. Clin Transl Immunology 2021;10(8):e1318.
- Lai X, Kline JA, Wang M. Development, validation, and comparison of four methods to simultaneously quantify l-arginine, citrulline, and ornithine in human plasma using hydrophilic interaction liquid chromatography and electrospray tandem mass spectrometry.. J Chromatogr B Analyt Technol Biomed Life Sci 2015 Nov 15;1005:47-55.
- Yan J, Kuzhiumparambil U, Bandodkar A, Bandodkar S, Dale RC, Fu S. Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation.. Dev Med Child Neurol 2021 May;63(5):552-559.
- Eisenhofer G, Peitzsch M, Kaden D, Langton K, Mangelis A, Pamporaki C, Masjkur J, Geroula A, Kurlbaum M, Deutschbein T, Beuschlein F, Prejbisz A, Bornstein SR, Lenders JWM. Reference intervals for LC-MS/MS measurements of plasma free, urinary free and urinary acid-hydrolyzed deconjugated normetanephrine, metanephrine and methoxytyramine.. Clin Chim Acta 2019 Mar;490:46-54.
- Collino S, Martin FP, Rezzi S. Clinical metabolomics paves the way towards future healthcare strategies.. Br J Clin Pharmacol 2013 Mar;75(3):619-29.
- Christou C, Gika HG, Raikos N, Theodoridis G. GC-MS analysis of organic acids in human urine in clinical settings: a study of derivatization and other analytical parameters.. J Chromatogr B Analyt Technol Biomed Life Sci 2014 Aug 1;964:195-201.
- Szeremeta M, Pietrowska K, Niemcunowicz-Janica A, Kretowski A, Ciborowski M. Applications of Metabolomics in Forensic Toxicology and Forensic Medicine.. Int J Mol Sci 2021 Mar 16;22(6).
- Busardò FP, Kyriakou C, Marchei E, Pacifici R, Pedersen DS, Pichini S. Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for determination of GHB, precursors and metabolites in different specimens: Application to clinical and forensic cases.. J Pharm Biomed Anal 2017 Apr 15;137:123-131.
- Petersen IN, Tortzen C, Kristensen JL, Pedersen DS, Breindahl T. Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide.. J Anal Toxicol 2013 Jun;37(5):291-7.
- Pascali JP, Fais P, Vaiano F, Ciolini A, Bertol E. Zwitterionic HILIC stationary phase as a valuable alternative in separative techniques: Application to the analysis of gamma-hydroxybutyric acid and its metabolite in hair.. J Chromatogr B Analyt Technol Biomed Life Sci 2019 Dec 15;1134-1135:121876.
- Steuer AE, Raeber J, Steuer C, Boxler MI, Dornbierer DA, Bosch OG, Quednow BB, Seifritz E, Kraemer T. Identification of new urinary gamma-hydroxybutyric acid markers applying untargeted metabolomics analysis following placebo-controlled administration to humans.. Drug Test Anal 2019 Jun;11(6):813-823.
- Eisenbeiss L, Binz TM, Baumgartner MR, Kraemer T, Steuer AE. Towards Best Practice in Hair Metabolomic Studies: Systematic Investigation on the Impact of Hair Length and Color.. Metabolites 2020 Sep 26;10(10).
- Eisenbeiss L, Binz TM, Baumgartner MR, Steuer AE, Kraemer T. A possible new oxidation marker for hair adulteration: Detection of PTeCA (1H-pyrrole-2,3,4,5-tetracarboxylic acid) in bleached hair.. Drug Test Anal 2020 Feb;12(2):230-238.
- Madry MM, Kraemer T, Baumgartner MR. Large scale consumption monitoring of benzodiazepines and z-drugs by hair analysis.. J Pharm Biomed Anal 2020 May 10;183:113151.
- Voegel CD, Hofmann M, Kraemer T, Baumgartner MR, Binz TM. Endogenous steroid hormones in hair: Investigations on different hair types, pigmentation effects and correlation to nails.. Steroids 2020 Feb;154:108547.
- Zhou Y, Xie Z, Zhang Z, Yang J, Chen M, Chen F, Ma Y, Chen C, Peng Q, Zou L, Gao J, Xu Y, Kuang Y, Zhu M, You D, Yu J, Wang K. Plasma metabolites changes in male heroin addicts during acute and protracted withdrawal.. Aging (Albany NY) 2021 Jul 19;13(14):18669-18688.
- Steuer AE, Kaelin D, Boxler MI, Eisenbeiss L, Holze F, Vizeli P, Czerwinska J, Dargan PI, Abbate V, Liechti ME, Kraemer T. Comparative Untargeted Metabolomics Analysis of the Psychostimulants 3,4-Methylenedioxy-Methamphetamine (MDMA), Amphetamine, and the Novel Psychoactive Substance Mephedrone after Controlled Drug Administration to Humans.. Metabolites 2020 Jul 27;10(8).
- Eisenbeiss L, Binz TM, Baumgartner MR, Kraemer T, Steuer AE. Cheating on forensic hair testing? Detection of potential biomarkers for cosmetically altered hair samples using untargeted hair metabolomics.. Analyst 2020 Oct 12;145(20):6586-6599.
- Steuer AE, Arnold K, Kamber D, Kraemer T. Suitability evaluation of new endogenous biomarkers for the identification of nitrite-based urine adulteration in mass spectrometry methods.. Drug Test Anal 2019 Feb;11(2):230-239.
- Schumacher YO, Garvican LA, Christian R, Lobigs LM, Qi J, Fan R, He Y, Wang H, Gore CJ, Ma F. High altitude, prolonged exercise, and the athlete biological passport.. Drug Test Anal 2015 Jan;7(1):48-55.
- Athanasiadou I, Angelis YS, Lyris E, Georgakopoulos C. Chemical derivatization to enhance ionization of anabolic steroids in LC‐MS for doping‐control analysis. TrAC 2013;42:137‐156.
- Raro M, Ibáñez M, Gil R, Fabregat A, Tudela E, Deventer K, Ventura R, Segura J, Marcos J, Kotronoulas A, Joglar J, Farré M, Yang S, Xing Y, Van Eenoo P, Pitarch E, Hernández F, Sancho JV, Pozo ÓJ. Untargeted metabolomics in doping control: detection of new markers of testosterone misuse by ultrahigh performance liquid chromatography coupled to high-resolution mass spectrometry.. Anal Chem 2015 Aug 18;87(16):8373-80.
- Boccard J, Badoud F, Grata E, Ouertani S, Hanafi M, Mazerolles G, Lantéri P, Veuthey JL, Saugy M, Rudaz S. A steroidomic approach for biomarkers discovery in doping control.. Forensic Sci Int 2011 Dec 10;213(1-3):85-94.
- Palermo A, Botrè F, de la Torre X, Zamboni N. Non-targeted LC-MS based metabolomics analysis of the urinary steroidal profile.. Anal Chim Acta 2017 Apr 29;964:112-122.
- Narduzzi L, Dervilly G, Marchand A, Audran M, Le Bizec B, Buisson C. Applying metabolomics to detect growth hormone administration in athletes: Proof of concept.. Drug Test Anal 2020 Jul;12(7):887-899.
- Cawley AT, Keledjian J. Intelligence-based anti-doping from an equine biological passport.. Drug Test Anal 2017 Sep;9(9):1441-1447.
- Vernec AR. The Athlete Biological Passport: an integral element of innovative strategies in antidoping.. Br J Sports Med 2014 May;48(10):817-9.
- Sottas P‐E, Robinson N, Saugy M, Niggli O. A forensic approach to the interpretation of blood doping markers. Law, probability and risk 2008;7(3):191‐210.
- Wilkin T, Baoutina A, Hamilton N. Equine performance genes and the future of doping in horseracing.. Drug Test Anal 2017 Sep;9(9):1456-1471.
- Yuan M, Breitkopf SB, Asara JM. Serial-omics characterization of equine urine.. PLoS One 2017;12(10):e0186258.
- Le Moyec L, Robert C, Triba MN, Billat VL, Mata X, Schibler L, Barrey E. Protein catabolism and high lipid metabolism associated with long-distance exercise are revealed by plasma NMR metabolomics in endurance horses.. PLoS One 2014;9(3):e90730.
- Jang HJ, Kim DM, Kim KB, Park JW, Choi JY, Oh JH, Song KD, Kim S, Cho BW. Analysis of metabolomic patterns in thoroughbreds before and after exercise.. Asian-Australas J Anim Sci 2017 Nov;30(11):1633-1642.
- Mach N, Ramayo-Caldas Y, Clark A, Moroldo M, Robert C, Barrey E, López JM, Le Moyec L. Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNomics in horses.. BMC Genomics 2017 Feb 17;18(1):187.
- Kieken F, Pinel G, Antignac J‐P. Generation and processing of urinary and plasmatic metabolomic fingerprints to reveal an illegal administration of recombinant equine growth hormone from LC‐HRMS measurements. Metabolomics 2011;7(1):84‐93.
- Stanley S, Van den Berg K, Foo HC, Deng D. Metabolism and elimination of the catechol-o-methyltransferase inhibitor tolcapone in the horse.. Drug Test Anal 2019 Apr;11(4):578-585.
- McKinney A, Richards S, Cawley A, Keledjian J, Wynne P, Suann CJ. Catechol‐O‐methyltransferase inhibitors and the equine 3‐methoxytyramine threshold. 20th Int Conf Racing Anal Vets 2015;295‐299.
- Wynne PM, Vine JH, Amiet RG. 3-Methoxytyramine as an indicator of dopaminergic manipulation in the equine athlete.. J Chromatogr B Analyt Technol Biomed Life Sci 2004 Nov 5;811(1):93-101.
- Caprioli G, Genangeli M, Mustafa AM, Petrelli R, Ricciutelli M, Sagratini G, Sartori S, Laus F, Vittori S, Cortese M. Quantification of 17 Endogenous and Exogenous Steroidal Hormones in Equine and Bovine Blood for Doping Control with UHPLC-MS/MS.. Pharmaceuticals (Basel) 2021 Apr 21;14(5).
- Kaabia Z, Dervilly-Pinel G, Popot MA, Bailly-Chouriberry L, Plou P, Bonnaire Y, Le Bizec B. Monitoring the endogenous steroid profile disruption in urine and blood upon nandrolone administration: An efficient and innovative strategy to screen for nandrolone abuse in entire male horses.. Drug Test Anal 2014 Apr;6(4):376-88.
- Chan GH, Ho EN, Leung DK, Wong KS, Wan TS. Targeted Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker Profiling.. Anal Chem 2016 Jan 5;88(1):764-72.
- Stucki M, Voegel CD, Binz TM, Kraemer T, Lavaud A, Voelter K. Systemic detectability of dexamethasone and prednisolone after eye drop application in horses.. Equine Vet J 2021 Nov;53(6):1250-1256.
- Joré C, Loup B, Garcia P, Paris AC, Popot MA, Audran M, Bonnaire Y, Varlet-Marie E, Bailly-Chouriberry L. Liquid chromatography - high resolution mass spectrometry-based metabolomic approach for the detection of Continuous Erythropoiesis Receptor Activator effects in horse doping control.. J Chromatogr A 2017 Oct 27;1521:90-99.
- Riedmaier I, Becker C, Pfaffl MW, Meyer HH. The use of omic technologies for biomarker development to trace functions of anabolic agents.. J Chromatogr A 2009 Nov 13;1216(46):8192-9.
- Courant F, Pinel G, Bichon E, Monteau F, Antignac JP, Le Bizec B. Development of a metabolomic approach based on liquid chromatography-high resolution mass spectrometry to screen for clenbuterol abuse in calves.. Analyst 2009 Aug;134(8):1637-46.
- Dervilly-Pinel G, Royer AL, Bozzetta E, Pezzolato M, Herpin L, Prevost S, Le Bizec B. When LC-HRMS metabolomics gets ISO17025 accredited and ready for official controls - application to the screening of forbidden compounds in livestock.. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2018 Oct;35(10):1948-1958.
- Dervilly-Pinel G, Courant F, Chéreau S, Royer AL, Boyard-Kieken F, Antignac JP, Monteau F, Le Bizec B. Metabolomics in food analysis: application to the control of forbidden substances.. Drug Test Anal 2012 Aug;4 Suppl 1:59-69.
- Nebbia C, Urbani A, Carletti M, Gardini G, Balbo A, Bertarelli D, Girolami F. Novel strategies for tracing the exposure of meat cattle to illegal growth-promoters.. Vet J 2011 Jul;189(1):34-42.
- Cacciatore G, Eisenberg SW, Situ C, Mooney MH, Delahaut P, Klarenbeek S, Huet AC, Bergwerff AA, Elliott CT. Effect of growth-promoting 17beta-estradiol, 19-nortestosterone and dexamethasone on circulating levels of nine potential biomarker candidates in veal calves.. Anal Chim Acta 2009 Apr 1;637(1-2):351-9.
- Nzoughet JK, Gallart‐Ayala H, Biancotto G, Hennig K, Dervilly‐Pinel G, Le Bizec B. Hydrophilic interaction (HILIC) and reverse phase liquid chromatography (RPLC)–high resolution MS for characterizing lipids profile disruption in serum of anabolic implanted bovines. Metabolomics 2015;11(6):1884‐1895.
Citations
This article has been cited 5 times.- Meng S, Zhang Y, Lv S, Zhang Z, Liu X, Jiang L. Comparison of muscle metabolomics between two Chinese horse breeds. Front Vet Sci 2023;10:1162953.
- Wissenbach DK, Steuer AE. Advances in testing for sample manipulation in clinical and forensic toxicology - Part A: urine samples. Anal Bioanal Chem 2023 Sep;415(21):5101-5115.
- Main SC, Brown LP, Melvin KR, Campagna SR, Voy BH, Castro HF, Strickland LG, Hines MT, Jacobs RD, Gordon ME, Ivey JLZ. Metabolomic Profiles in Starved Light Breed Horses during the Refeeding Process. Animals (Basel) 2022 Sep 21;12(19).
- Elbourne M, Keledjian J, Cawley A, Fu S. Administration Route Differentiation of Altrenogest via the Metabolomic LC-HRMS Analysis of Equine Urine. Molecules 2024 Oct 22;29(21).
- Camelo ALM, Zamora Obando HR, Rocha I, Dias AC, Mesquita AS, Simionato AVC. COVID-19 and Comorbidities: What Has Been Unveiled by Metabolomics?. Metabolites 2024 Mar 30;14(4).
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