Open Access Open Access  Restricted Access Subscription or Fee Access

Analytical Techniques Used In Metabolomic Analysis

Saurabh S. Avhad, Yogeshwari Ambekr, Hemant Chikhale, Laxmikant Borse, Sreya Kosanam

Abstract


Comprehensive studies regarding metabolomics provides us ample of information about the structural properties and various other parameters pertaining to the molecule under study. Metabolomics is employed for managing long-term illness such as cancer, diabetes. It’s applications also stretch to treating diseases such as tachycardia along with various cardiovascular diseases. It is used to treat inborn errors of metabolism which are found out in infants. These molecules along with processes of metabolism may be separated from one another, detected, characterized, and quantified with respect to current and swift growth of a variety of testing systems including gas chromatography, High-performance liquid chromatography connected to Mass spectrometry and Nuclear Magnetic Resonance spectroscopy. The optimal results in metabolomics have been shown by using a combination of contemporary instrumental analytical approaches, and it is advantageous for increasing the limitations with regards to observed substances that are not able to accomplished through solitary-analysis procedures. A biofluid specimen can contain several thousand substances and these substances have frequently been detected sensitively and accurately using combined technologies. The broad acceptance and incorporation of metabolomics into biological systems will be accelerated by the continued growth of these analytical techniques. Here, the use of each punctuated methodology is explained, along with its benefits and drawbacks, using particular illustrations. Additionally, the article thoroughly emphasizes the use of comprehensive instruments in metabolomic analysis. The independent and untargeted examination of cell metabolites in specimen samples is known as metabolomics, and it can be seen as an evolutionary change in the field of analytical biochemistry which took place in the post-genomic period. For many years, the study of metabolites has been a crucial component of life science, helping to create techniques for disease diagnosis, phenotypic assessment of varieties and breeds, assurance of the quality for agricultural items, and investigation of the bodily functions of multiple microorganisms. The genomic revolution, which made the genome sequences of entire biological systems available, along with technological advancements in analytical chemistry, however, compelled us to revisit the methods used to analyse metabolites in samples of various life forms. The study of natural metabolites in its whole, or metabolomics, aims to thoroughly recognize and calculate metabolites in a specimen substance. Miniscule-molecule metabolites are intriguing options for understanding the characteristics of diseases because of their significant roles in biological mechanisms.

Keywords


Metabolomics, Lipids, Peptides, Analysis, Biological Sample.

Full Text:

PDF

References


Nicholson JK, Lindon JC. Metabonomics. Nature. 2008 Oct 23;455(7216):1054-6.

Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon JC, Mitchell SC. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proceedings of the national academy of sciences. 2006 Aug 15;103(33):12511-6.

Wang X, Sun H, Zhang A, Sun W, Wang P, Wang Z. Potential role of metabolomics apporoaches in the area of traditional Chinese medicine: as pillars of the bridge between Chinese and Western medicine. Journal of pharmaceutical and biomedical analysis. 2011 Jul 15;55(5):859-68.

Zhang A, Sun H, Wang Z, Sun W, Wang P, Wang X. Metabolomics: towards understanding traditional Chinese medicine. Planta medica. 2010 Dec;76(17):2026-35.

Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.

Arakaki AK, Skolnick J, McDonald JF. Marker metabolites can be therapeutic targets as well. Nature. 2008 Nov 27;456(7221):443-.

Villas-Bôas SG, Rasmussen S, Lane GA. Metabolomics or metabolite profiles. trends in Biotechnology. 2005 Aug 1;23(8):385-6.

Reaves ML, Rabinowitz JD. Metabolomics in systems microbiology. Current opinion in biotechnology. 2011 Feb 1;22(1):17-25.

McCartney A, Vignoli A, Biganzoli L, Love R, Tenori L, Luchinat C, Di Leo A. Metabolomics in breast cancer: A decade in review. Cancer Treatment Reviews. 2018 Jun 1;67:88-96.

Markley JL, Brüschweiler R, Edison AS, Eghbalnia HR, Powers R, Raftery D, Wishart DS. The future of NMR-based metabolomics. Current opinion in biotechnology. 2017 Feb 1;43:34-40.

Liu C, Wang Z, Hui Q, Chiang Y, Chen J, Brijkumar J, Edwards JA, Ordonez CE, Dudgeon MR, Sunpath H, Pillay S. Crosstalk between Host Genome and Metabolome among People with HIV in South Africa. Metabolites. 2022 Jul 6;12(7):624.

Shi X, Wang S, Jasbi P, Turner C, Hrovat J, Wei Y, Liu J, Gu H. Database-assisted globally optimized targeted mass spectrometry (dGOT-MS): broad and reliable metabolomics analysis with enhanced identification. Analytical chemistry. 2019 Sep 26;91(21):13737-45.

Clish CB. Metabolomics: an emerging but powerful tool for precision medicine. Molecular Case Studies. 2015 Oct 1;1(1):a000588.

van den Brink W, van Bilsen J, Salic K, Hoevenaars FP, Verschuren L, Kleemann R, Bouwman J, Ronnett GV, van Ommen B, Wopereis S. Current and future nutritional strategies to modulate inflammatory dynamics in metabolic disorders. Frontiers in Nutrition. 2019:129.

Martens J, Berden G, van Outersterp RE, Kluijtmans LA, Engelke UF, van Karnebeek CD, Wevers RA, Oomens J. Molecular identification in metabolomics using infrared ion spectroscopy. Scientific reports. 2017 Jun 13;7(1):3363.

Martens J, Berden G, van Outersterp RE, Kluijtmans LA, Engelke UF, van Karnebeek CD, Wevers RA, Oomens J. Molecular identification in metabolomics using infrared ion spectroscopy. Scientific reports. 2017 Jun 13;7(1):3363.

Yanes O, Tautenhahn R, Patti GJ, Siuzdak G. Expanding coverage of the metabolome for global metabolite profiling. Analytical chemistry. 2011 Mar 15;83(6):2152-61.

Cao DS, Wang B, Zeng MM, Liang YZ, Xu QS, Zhang LX, Li HD, Hu QN. A new strategy of exploring metabolomics data using Monte Carlo tree. Analyst. 2011;136(5):947-54.

Kim DH, Jarvis RM, Xu Y, Oliver AW, Allwood JW, Hampson L, Hampson IN, Goodacre R. Combining metabolic fingerprinting and footprinting to understand the phenotypic response of HPV16 E6 expressing cervical carcinoma cells exposed to the HIV anti-viral drug lopinavir. Analyst. 2010;135(6):1235-44.

Ding J, Yang S, Liang D, Chen H, Wu Z, Zhang L, Ren Y. Development of extractive electrospray ionization ion trap mass spectrometry for in vivo breath analysis. Analyst. 2009;134(10):2040-50.

Johnson CH, Karlsson E, Sarda S, Iddon L, Iqbal M, Meng X, Harding JR, Stachulski AV, Nicholson JK, Wilson ID, Lindon JC. Integrated HPLC-MS and 1H-NMR spectroscopic studies on acyl migration reaction kinetics of model drug ester glucuronides. Xenobiotica. 2010 Jan 1;40(1):9-23.

Kim K, Aronov P, Zakharkin SO, Anderson D, Perroud B, Thompson IM, Weiss RH. Urine metabolomics analysis for kidney cancer detection and biomarker discovery. Molecular & cellular proteomics. 2009 Mar 1;8(3):558-70.

Liu H, Zheng A, Liu H, Yu H, Wu X, Xiao C, Dai H, Hao F, Zhang L, Wang Y, Tang H. Identification of three novel polyphenolic compounds, origanine A–C, with unique skeleton from Origanum vulgare L. using the hyphenated LC-DAD-SPE-NMR/MS methods. Journal of agricultural and food chemistry. 2012 Jan 11;60(1):129-35.

Reaves ML, Rabinowitz JD. Metabolomics in systems microbiology. Current opinion in biotechnology. 2011 Feb 1;22(1):17-25.

Emwas AH, Roy R, McKay RT, Tenori L, Saccenti E, Gowda GN, Raftery D, Alahmari F, Jaremko L, Jaremko M, Wishart DS. NMR spectroscopy for metabolomics research. Metabolites. 2019 Jun 27;9(7):123.

Stoop MP, Coulier L, Rosenling T, Shi S, Smolinska AM, Buydens L, Ampt K, Stingl C, Dane A, Muilwijk B, Luitwieler RL. Quantitative proteomics and metabolomics analysis of normal human cerebrospinal fluid samples. Molecular & Cellular Proteomics. 2010 Sep 1;9(9):2063-75.

Park JM, Kim TY, Lee SY. Prediction of metabolic fluxes by incorporating genomic context and flux-converging pattern analyses. Proceedings of the National Academy of Sciences. 2010 Aug 17;107(33):14931-6.

Liu H, Zheng A, Liu H, Yu H, Wu X, Xiao C, Dai H, Hao F, Zhang L, Wang Y, Tang H. Identification of three novel polyphenolic compounds, origanine A–C, with unique skeleton from Origanum vulgare L. using the hyphenated LC-DAD-SPE-NMR/MS methods. Journal of agricultural and food chemistry. 2012 Jan 11;60(1):129-35.

Wu J, An Y, Yao J, Wang Y, Tang H. An optimised sample preparation method for NMR-based faecal metabonomic analysis. Analyst. 2010;135(5):1023-30.

Soininen P, Kangas AJ, Würtz P, Tukiainen T, Tynkkynen T, Laatikainen R, Järvelin MR, Kähönen M, Lehtimäki T, Viikari J, Raitakari OT. High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism. Analyst. 2009;134(9):1781-5.

Zhang S, Gowda GN, Ye T, Raftery D. Advances in NMR-based biofluid analysis and metabolite profiling. Analyst. 2010;135(7):1490-8.

Malet-Martino M, Holzgrabe U. NMR techniques in biomedical and pharmaceutical analysis. Journal of pharmaceutical and biomedical analysis. 2011 Apr 28;55(1):1-5.

G. Liu, Y. Wang, Z. Wang, J. Cai, X. Lv and A. Zhou, J Agric Food Chem., 2011, 59, 5572–5578

Jung JY, Lee HS, Kang DG, Kim NS, Cha MH, Bang OS. H. Ryu do and GS Hwang. Stroke. 2011;42:1282-8.

Barba I, Fernandez‐Montesinos R, Garcia‐Dorado D, Pozo D. Alzheimer's disease beyond the genomic era: nuclear magnetic resonance (NMR) spectroscopy‐based metabolomics. Journal of cellular and molecular medicine. 2008 Sep;12(5a):1477-85.

Jordan KW, Cheng LL. NMR-based metabolomics approach to target biomarkers for human prostate cancer. Expert Review of Proteomics. 2007 Jun 1;4(3):389-400.

Siuzdak G. The expanding role of mass spectrometry in biotechnology. (No Title). 2006.

Johnson CH, Ivanisevic J, Benton HP, Siuzdak G. Bioinformatics: the next frontier of metabolomics. Analytical Chemistry. 2015 Jan 6;87(1):147-56.

Kraft ML, Weber PK, Longo ML, Hutcheon ID, Boxer SG. Phase separation of lipid membranes analyzed with high-resolution secondary ion mass spectrometry. Science. 2006 Sep 29;313(5795):1948-51.

Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T, Matsuo TJ. Protein and polymer analyses up to m/z 100 000 by laser ionization time‐of‐flight mass spectrometry. Rapid communications in mass spectrometry. 1988 Aug;2(8):151-3.

Hiller K, Metallo CM, Kelleher JK, Stephanopoulos G. Nontargeted elucidation of metabolic pathways using stable-isotope tracers and mass spectrometry. Analytical chemistry. 2010 Aug 1;82(15):6621-8.

Weston DJ. Ambient ionization mass spectrometry: current understanding of mechanistic theory; analytical performance and application areas. Analyst. 2010;135(4):661-8.

Tsugawa H, Bamba T, Shinohara M, Nishiumi S, Yoshida M, Fukusaki E. Practical non-targeted gas chromatography/mass spectrometry-based metabolomics platform for metabolic phenotype analysis. Journal of bioscience and bioengineering. 2011 Sep 1;112(3):292-8.

Zhang A, Sun H, Wang P, Han Y, Wang X. Modern analytical techniques in metabolomics analysis. Analyst. 2012;137(2):293-300.

Cooper AJ, Kuhara T. α-Ketoglutaramate: an overlooked metabolite of glutamine and a biomarker for hepatic encephalopathy and inborn errors of the urea cycle. Metabolic brain disease. 2014 Dec;29:991-1006.

Barbas C, Moraes EP, Villasenor A. Capillary electrophoresis as a metabolomics tool for non-targeted fingerprinting of biological samples. Journal of pharmaceutical and biomedical analysis. 2011 Jun 25;55(4):823-31.

Kuehnbaum NL, Britz-McKibbin P. New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era. Chemical reviews. 2013 Apr 10;113(4):2437-68.

Weber RJ, Southam AD, Sommer U, Viant MR. Characterization of isotopic abundance measurements in high resolution FT-ICR and Orbitrap mass spectra for improved confidence of metabolite identification. Analytical chemistry. 2011 May 15;83(10):3737-43.

Sato S, Arita M, Soga T, Nishioka T, Tomita M. Time-resolved metabolomics reveals metabolic modulation in rice foliage. BMC systems biology. 2008 Dec;2(1):1-3.

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;134(8):1637-46.

Denery JR, Nunes AA, Hixon MS, Dickerson TJ, Janda KD. PLoS Neglected Trop. InDis 2010 (Vol. 4, p. e834).

Chen J, Zhang X, Cao R, Lu X, Zhao S, Fekete A, Huang Q, Schmitt-Kopplin P, Wang Y, Xu Z, Wan X. Serum 27-nor-5β-cholestane-3, 7, 12, 24, 25 pentol glucuronide discovered by metabolomics as potential diagnostic biomarker for epithelium ovarian cancer. Journal of proteome research. 2011 May 6;10(5):2625-32.

Lv H, Palacios G, Hartil K, Kurland IJ. Advantages of tandem LC− MS for the rapid assessment of tissue-specific metabolic complexity using a pentafluorophenylpropyl stationary phase. Journal of proteome research. 2011 Apr 1;10(4):2104-12.

Ellinger-Ziegelbauer H, Adler M, Amberg A, Brandenburg A, Callanan JJ, Connor S, Fountoulakis M, Gmuender H, Gruhler A, Hewitt P, Hodson M. The enhanced value of combining conventional and “omics” analyses in early assessment of drug-induced hepatobiliary injury. Toxicology and applied pharmacology. 2011 Apr 15;252(2):97-111.

Want EJ, Masson P, Michopoulos F, Wilson ID, Theodoridis G, Plumb RS, Shockcor J, Loftus N, Holmes E, Nicholson JK. Global metabolic profiling of animal and human tissues via UPLC-MS. Nature protocols. 2013 Jan;8(1):17-32.

Dunn WB, Bailey NJ, Johnson HE. Measuring the metabolome: current analytical technologies. Analyst. 2005;130(5):606-25.

Su ZH, Li SQ, Zou GA, Yu CY, Sun YG, Zhang HW, Gu Y, Zou ZM. Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats. Journal of pharmaceutical and biomedical analysis. 2011 Jun 1;55(3):533-9.

Lu X, Xiong Z, Li J, Zheng S, Huo T, Li F. Metabonomic study on ‘Kidney-Yang Deficiency syndrome’and intervention effects of Rhizoma Drynariae extracts in rats using ultra performance liquid chromatography coupled with mass spectrometry. Talanta. 2011 Jan 15;83(3):700-8.

Mohler RE, Dombek KM, Hoggard JC, Pierce KM, Young ET, Synovec RE. Comprehensive analysis of yeast metabolite GC× GC–TOFMS data: combining discovery-mode and deconvolution chemometric software. Analyst. 2007;132(8):756-67.

Goodpaster AM, Ramadas EH, Kennedy MA. Potential effect of diaper and cotton ball contamination on NMR-and LC/MS-based metabonomics studies of urine from newborn babies. Analytical chemistry. 2011 Feb 1;83(3):896-902.

Gao P, Lu C, Zhang F, Sang P, Yang D, Li X, Kong H, Yin P, Tian J, Lu X, Lu A. Integrated GC–MS and LC–MS plasma metabonomics analysis of ankylosing spondylitis. Analyst. 2008;133(9):1214-20.

An Z, Chen Y, Zhang R, Song Y, Sun J, He J, Bai J, Dong L, Zhan Q, Abliz Z. Integrated ionization approach for RRLC− MS/MS-based metabonomics: finding potential biomarkers for lung cancer. Journal of Proteome Research. 2010 Aug 6;9(8):4071-81.

Geier FM, Leroi AM, Bundy JG. 13C labeling of nematode worms to improve metabolome coverage by heteronuclear nuclear magnetic resonance experiments. Frontiers in Molecular Biosciences. 2019 Apr 26;6:27.

Wu Z, Li M, Zhao C, Zhou J, Chang Y, Li X, Gao P, Lu X, Li Y, Xu G. Urinary metabonomics study in a rat model in response to protein-energy malnutrition by using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Molecular BioSystems. 2010;6(11):2157-63.

Lin Y, Schiavo S, Orjala J, Vouros P, Kautz R. Microscale LC-MS-NMR platform applied to the identification of active cyanobacterial metabolites. Analytical chemistry. 2008 Nov 1;80(21):8045-54.

Johnson CH, Patterson AD, Krausz KW, Lanz C, Kang DW, Luecke H, Gonzalez FJ, Idle JR. Radiation metabolomics. 4. UPLC-ESI-QTOFMS-Based metabolomics for urinary biomarker discovery in gamma-irradiated rats. Radiation research. 2011 Apr 1;175(4):473-84.

C. Scherling, C. Roscher, P. Giavalisco, E. D. Schulze and W. Weckwerth, PLoS One, 2010, 5, e12569

Roach PD, Ketterson JB, Roach PR. Preliminary Measurements of the Low Temperature Ion Mobility in Normal Liquid 3 He. Quantum Fluids and Solids. 1977:259-64.

Ibrahim YM, Baker ES, Danielson WF et al. Development of a new ion mobility time-of-flight mass spectrometer. Int. J. Mass Spectrom.377, 655–662 (2015).

Gabelica V, Marklund E. Fundamentals of ion mobility spectrometry. Current opinion in chemical biology. 2018 Feb 1;42:51-9.

Tebani A, Schmitz-Afonso I, Rutledge DN, Gonzalez BJ, Bekri S, Afonso C. Optimization of a liquid chromatography ion mobility-mass spectrometry method for untargeted metabolomics using experimental design and multivariate data analysis. Analytica chimica acta. 2016 Mar 24;913:55-62.

Fenn LS, McLean JA. Structural separations by ion mobility-MS for glycomics and glycoproteomics. Mass Spectrometry of Glycoproteins: Methods and Protocols. 2013:171-94.

Chen Z, Glover MS, Li L. Recent advances in ion mobility–mass spectrometry for improved structural characterization of glycans and glycoconjugates. Current opinion in chemical biology. 2018 Feb 1;42:1-8.

Kanu AB, Dwivedi P, Tam M, Matz L, Hill Jr HH. Ion mobility–mass spectrometry. Journal of mass spectrometry. 2008 Jan;43(1):1-22.

Dodds JN, Baker ES. Ion mobility spectrometry: fundamental concepts, instrumentation, applications, and the road ahead. Journal of the American Society for Mass Spectrometry. 2019 Sep 6;30(11):2185-95.

Shulaev V, Isaac G. Supercritical fluid chromatography coupled to mass spectrometry–A metabolomics perspective. Journal of Chromatography B. 2018 Aug 15;1092:499-505.

Xia T, Fu S, Wang Q, Wen Y, Chan SA, Zhu S, Gao S, Tao X, Zhang F, Chen W. Targeted metabolomic analysis of 33 amino acids and biogenic amines in human urine by ion‐pairing HPLC‐MS/MS: Biomarkers for tacrolimus nephrotoxicity after renal transplantation. Biomedical Chromatography. 2018 Jul;32(7):e4198.

Pferschy-Wenzig EM, Koskinen K, Moissl-Eichinger C, Bauer R. A Combined LC-MS Metabolomics-and 16S rRNA sequencing platform to assess interactions between herbal medicinal products and human gut bacteria in vitro: A pilot study on willow bark extract. Frontiers in pharmacology. 2017 Dec 13;8:893.

Samczuk P, Hady HR, Adamska-Patruno E, Citko A, Dadan J, Barbas C, Kretowski A, Ciborowski M. In-and-out molecular changes linked to the type 2 diabetes remission after bariatric surgery: an influence of gut microbes on mitochondria metabolism. International journal of molecular sciences. 2018 Nov 24;19(12):3744.

Giera M, Kaisar MM, Derks RJ, Steenvoorden E, Kruize YC, Hokke CH, Yazdanbakhsh M, Everts B. The Schistosoma mansoni lipidome: Leads for immunomodulation. Analytica Chimica Acta. 2018 Dec 11;1037:107-18.

Liu W, Song Q, Cao Y, Zhao Y, Huo H, Wang Y, Song Y, Li J, Tu P. Advanced liquid chromatography-mass spectrometry enables merging widely targeted metabolomics and proteomics. Analytica Chimica Acta. 2019 Sep 3;1069:89-97.

Wang S, Zhou L, Wang Z, Shi X, Xu G. Simultaneous metabolomics and lipidomics analysis based on novel heart-cutting two-dimensional liquid chromatography-mass spectrometry. Analytica chimica acta. 2017 May 8;966:34-40.

Daskapan A, van Hateren K, Stienstra Y, Kosterink J, van der Werf T, Touw D, Alffenaar JW. Development and validation of a bioanalytical method for the simultaneous determination of 14 antiretroviral drugs using liquid chromatography-tandem mass spectrometry. J Appl Bioanal. 2018;4(2):32-45.

Naz S, Garcia A, Rusak M, Barbas C. Method development and validation for rat serum fingerprinting with CE–MS: application to ventilator-induced-lung-injury study. Analytical and bioanalytical chemistry. 2013 May;405:4849-58.

Begou O, Gika HG, Theodoridis GA, Wilson ID. Quality control and validation issues in LC-MS metabolomics. Metabolic profiling: Methods and protocols. 2018:15-26.

Jacob M, Malkawi A, Albast N, Al Bougha S, Lopata A, Dasouki M, Rahman AM. A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism. Analytica chimica acta. 2018 Sep 26;1025:141-53.

J Hunter D, Losina E, Guermazi A, Burstein D, N Lassere M, Kraus V. A pathway and approach to biomarker validation and qualification for osteoarthritis clinical trials. Current drug targets. 2010 May 1;11(5):536-45.

Beger RD, Dunn WB, Bandukwala A, Bethan B, Broadhurst D, Clish CB, Dasari S, Derr L, Evans A, Fischer S, Flynn T. Towards quality assurance and quality control in untargeted metabolomics studies. Metabolomics. 2019 Jan;15:1-5.

Lacorte S, Fernandez‐Alba AR. Time of flight mass spectrometry applied to the liquid chromatographic analysis of pesticides in water and food. Mass spectrometry reviews. 2006 Nov;25(6):866-80.

Arnaud CH. Supercritical fluid chromatography seeks new users. Chem. Eng. News. 2014;92(18):10-3.

Singh KS, Majik MS, Tilvi S. Vibrational spectroscopy for structural characterization of bioactive compounds. InComprehensive analytical chemistry 2014 Jan 1 (Vol. 65, pp. 115-148). Elsevier.




DOI: https://doi.org/10.37591/(rrjops).v14i3.1367

Refbacks

  • There are currently no refbacks.


Copyright (c) 2023 Research and Reviews: A Journal of Pharmaceutical Science