http://dx.doi.org/10.4322/sc.2017.018

 

Eletroforese capilar acoplada à espectrometria de massas (CE-MS): aspectos teóricos, práticos e aplicações no campo da metabolômica

Simionato, Ana Valéria Colnaghi; Santos, Fábio Neves dos; Hernandes, Vinicius Veri

Palavras-chave: eletroforese capilar acoplada a espectrometria de massas, metabolômica, fundamentos, avanços, aplicações.

ResumoHá três décadas, a eletroforese capilar foi acoplada pela primeira vez à espectrometria de massas. Desde então, o desenvolvimento de instrumentação e metodologias vem sendo aperfeiçoado e, impulsionado, principalmente, pelas aplicações no campo da metabolômica. As interfaces CE-MS são o centro dos recentes desenvolvimentos que tentam integrar ao máximo as vantagens da separação por eletroforese e da detecção e identificação pelos analisadores de espectrometria de massas, em uma única técnica de alta eficiência. Atualmente, CE-MS é considerada uma técnica em plena consolidação, devido o crescente número de usuários e grupos de pesquisas trabalhando com aplicações em diferentes áreas da ciência. Em particular, a metabolômica e suas aplicações em bioanalítica se destacam com o maior uso das diferentes técnicas e instrumentações de CE-MS em virtude da sua relevância para o estudo de doenças, nos diagnósticos e no entendimento dos mecanismos bioquímicos envolvidos nas patologias clínicas, mas também nas áreas de alimentos para segurança alimentar e valor nutricional, ambiental focado em poluentes e contaminantes emergentes. A abrangência das aplicações e a inserção em diferentes áreas da ciência revela a consolidação de CE-MS no campo da metabolômica.


Referências Bibliográficas

[1] Assunção NA, Bechara EJH, Simionato AVC, Tavares MFM, Carrilho E. Eletroforese capilar acoplada à espectrometria de massas (CE-MS): vinte anos de desenvolvimento. Química Nova. 2008;31:2124-33.
[2] Robledo VR, Smyth WF. Review of the CE-MS platform as a powerful alternative to conventional couplings in bio-omics and target-based applications. Electrophoresis. 2014;35(16):2292-308.
[3] Ramautar R, Somsen GW, de Jong GJ. CE-MS for metabolomics: Developments and applications in the period 2012–2014. Electrophoresis. 2015;36(1):212-24.
[4] Ramautar R, Somsen GW, de Jong GJ. CE-MS for metabolomics: Developments and applications in the period 2010–2012. Electrophoresis. 2013;34(1):86-98.
[5] Ramautar R, Somsen GW, de Jong GJ. CE–MS for metabolomics: Developments and applications in the period 2014–2016. Electrophoresis. 2017;38(1):190-202.
[6] Gulersonmez MC, Lock S, Hankemeier T, Ramautar R. Sheathless capillary electrophoresis-mass spectrometry for anionic metabolic profiling. Electrophoresis. 2016;37(7-8):1007-14.
[7] Olivares JA, Nguyen NT, Yonker CR, Smith RD. On-line mass spectrometric detection for capillary zone electrophoresis. Analytical Chemistry. 1987;59(8):1230-2.
[8] Tomlinson AJ, Benson LM, Gorrod JW, Naylor S. Investigation of the in vitro metabolism of the H2-antagonist mifentidine by on-line capillary electrophoresis—mass spectrometry using nonaqueous separation conditions. Journal of Chromatography B: Biomedical Sciences and Applications. 1994;657(2):373-81.
[9] Jäverfalk EM, Amini A, Westerlund D, Andrén PE. Chiral separation of local anaesthetics by a capillary electrophoresis/partial filling technique coupled on-line to micro-electrospray mass spectrometry. Journal of Mass Spectrometry. 1998;33(2):183-6.
[10] Ingendoh A, Kiehne A, Greiner M. CE-MS-MS of peptides using a novel orthogonal CE ESI sprayer andj ion trap MS. Chromatographia. 1999;49(1):S87-S92.
[11] Soga T, Ohashi Y, Ueno Y, Naraoka H, Tomita M, Nishioka T. Quantitative Metabolome Analysis Using Capillary Electrophoresis Mass Spectrometry. Journal of Proteome Research. 2003;2(5):488-94.
[12] Moini M. Simplifying CE−MS Operation. 2. Interfacing Low-Flow Separation Techniques to Mass Spectrometry Using a Porous Tip. Analytical Chemistry. 2007;79(11):4241-6.
[13] Wang C, Lee CS, Smith RD, Tang K. Capillary Isotachophoresis-Nanoelectrospray Ionization-Selected Reaction Monitoring MS via a Novel Sheathless Interface for High Sensitivity Sample Quantification. Analytical Chemistry. 2013;85(15):7308-15.
[14] Righetti PG. Electrophoresis: The march of pennies, the march of dimes. Journal of Chromatography A. 2005;1079(1):24-40.
[15] Mikkers FEP, Everaerts FM, Verheggen TPEM. High-performance zone electrophoresis. Journal of Chromatography A. 1979;169(Supplement C):11-20.
[16] Jorgenson JW, Lukacs KD. Zone electrophoresis in open-tubular glass capillaries. Analytical Chemistry. 1981;53(8):1298-302.
[17] Terabe S, Otsuka K, Ichikawa K, Tsuchiya A, Ando T. Electrokinetic separations with micellar solutions and open-tubular capillaries. Analytical Chemistry. 1984;56(1):111-3.
[18] Awdeh ZL, Williamson AR, Askonas BA. Isoelectric Focusing in Polyacrylamide Gel and its Application to Immunoglobulins. Nature. 1968;219:66.
[19] Martin AJP, Everaerts FM. Displacement electrophoresis. Analytica Chimica Acta. 1967;38:233-7.
[20] Pretorius V, Hopkins BJ, Schieke JD. Electro-osmosis: A new concept for high-speed liquid chromatography. Journal of Chromatography A. 1974;99(Supplement C):23-30.
[21] Grossbach U. Acrylamide gel electrophoresis in capillary columns. Biochimica et Biophysica Acta (BBA) – General Subjects. 1965;107(1):180-2.
[22] H. Lauer H, P. Rozing G. High Performance Capillary Electrophoresis. Germany: Agilent Technologies; 2009-2014.
[23] Alfonso Spudeit D, Danielli Dolzan M, Amadeu Micke G. Conceitos básicos em Eletroforese Capilar. Scientia Chromatographica. 2012;4(4):287-97.
[24] F. M. Tavares M. Mecanismos de Separação em Eletroforese Capilar. Química Nova. 1997;20(5):493- 511.
[25] Capillary Electrophoresis – Methods and Protocols. 2nd ed. Schimt-Kopplin P, editor: Humana Press; 2016.
[26] De Jong G. Capillary Electrophoresis-Mass Spectrometry (CE-MS): Principles and Applications: John Wiley & Sons; 2016.
[27] Ramautar R, Somsen GW, de Jong GJ. CE-MS in metabolomics. ELECTROPHORESIS. 2009;30(1):276- 91.
[28] Baker DR, Foret F. Capillary Electrophoresis: Techniques in Analytical Chemistry Series. Analytical Biochemistry. 1995;231(1):274.
[29] Landers JP. Handbook of capillary and microchip electrophoresis and associated microtechniques: CRC press; 2007.
[30] Zhang W, Hankemeier T, Ramautar R. Next-generation capillary electrophoresis–mass spectrometry approaches in metabolomics. Current Opinion in Biotechnology. 2017;43(Supplement C):1-7.
[31] Klepárník K. Recent advances in combination of capillary electrophoresis with mass spectrometry: Methodology and theory. Electrophoresis. 2015;36(1):159-78.
[32] Bonvin G, Schappler J, Rudaz S. Capillary electrophoresis–electrospray ionization-mass spectrometry interfaces: Fundamental concepts and technical developments. Journal of Chromatography A. 2012;1267(Supplement C):17-31.
[33] Konermann L, Ahadi E, Rodriguez AD, Vahidi S. Unraveling the Mechanism of Electrospray Ionization. Analytical Chemistry. 2013;85(1):2-9.
[34] Týčová A, Ledvina V, Klepárník K. Recent advances in CE-MS coupling: Instrumentation, methodology, and applications. Electrophoresis. 2017;38(1):115-34.
[35] Hashimoto M, Ishihama Y, Tomita M, Soga T. Microelectrospray interface with coaxial sheath flow for high-resolution capillary electrophoresis/mass spectrometry separation. Rapid Communications in Mass Spectrometry. 2007;21(22):3579-84.
[36] Pantůčková P, Gebauer P, Boček P, Křivánková L. Recent advances in CE-MS: Synergy of wet chemistry and instrumentation innovations. Electrophoresis. 2011;32(1):43-51.
[37] Yin Y, Li G, Guan Y, Huang G. Sheathless interface to match flow rate of capillary electrophoresis with electrospray mass spectrometry using regular-sized capillary. Rapid Communications in Mass Spectrometry. 2016;30:68-72.
[38] Zhong X, Maxwell EJ, Ratnayake C, Mack S, Chen DDY. Flow-Through Microvial Facilitating Interface of Capillary Isoelectric Focusing and Electrospray Ionization Mass Spectrometry. Analytical Chemistry. 2011;83(22):8748-55.
[39] Wang C, Tang K, Smith RD. Sheathless interface for coupling capillary electrophoresis with mass spectrometry. Google Patents; 2014.
[40] Robledo VR, Smyth WF. The application of CE-MS in the trace analysis of environmental pollutants and food contaminants. Electrophoresis. 2009;30(10):1647-60.
[41] Jeong J-S, Kim S-K, Park S-R. Amino acid analysis of dried blood spots for diagnosis of phenylketonuria using capillary electrophoresis-mass spectrometry equipped with a sheathless electrospray ionization interface. Analytical and Bioanalytical Chemistry. 2013;405(25):8063-72.
[42] Maráková K, Piešt’anský J, Veizerová L, Galba J, Dokupilová S, Havránek E, et al. Multidrug analysis of pharmaceutical and urine matrices by on-line coupled capillary electrophoresis and triple quadrupole mass spectrometry. Journal of Separation Science. 2013;36(11):1805-16.
[43] Erny GL, León C, Marina ML, Cifuentes A. Time of flight versus ion trap MS coupled to CE to analyse intact proteins. Journal of Separation Science . 2008; 31(10): 1810–18.
[44] Baidoo EEK, Benke PI, Neusüss C, Pelzing M, Kruppa G, Leary JA, et al. Capillary ElectrophoresisFourier Transform Ion Cyclotron Resonance Mass Spectrometry for the Identification of Cationic Metabolites via a pH-Mediated Stacking-Transient Isotachophoretic Method. Analytical Chemistry. 2008;80(9):3112-22.
[45] Kim J, Choi JN, John KMM, Kusano M, Oikawa A, Saito K, et al. GC–TOF-MS- and CE–TOF-MSBased Metabolic Profiling of Cheonggukjang (Fast-Fermented Bean Paste) during Fermentation and Its Correlation with Metabolic Pathways. Journal of Agricultural and Food Chemistry. 2012;60(38):9746- 53.
[46] Wojcik R, Li Y, Maccoss MJ, Dovichi NJ. Capillary electrophoresis with Orbitrap-Velos mass spectrometry detection. Talanta. 2012;88:324-9.
[47] Ramautar R, Somsen GW, de Jong GJ. Developments in coupled solid-phase extraction–capillary electrophoresis 2013–2015. Electrophoresis. 2016;37(1):35-44.
[48] Ferrer M, Raczkowska BA, Martínez-Martínez M, Barbas C, Rojo D. Phenotyping of gut microbiota: Focus on capillary electrophoresis. Electrophoresis. 2017;38(18):2275-86.
[49] Álvarez G, Montero L, Llorens L, Castro-Puyana M, Cifuentes A. Recent advances in the application of capillary electromigration methods for food analysis and Foodomics. Electrophoresis. 2014;35(1):147- 69.
[50] DiBattista A, Rampersaud D, Lee H, Kim M, Britz-McKibbin P. High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection–Capillary Electrophoresis–Mass Spectrometry. Analytical Chemistry. 2017;89(21):11853-61.
[51] Rodrigues KT, Cieslarová Z, Tavares MFM, Simionato AVC. Strategies Involving Mass Spectrometry Combined with Capillary Electrophoresis in Metabolomics. In: Sussulini A, editor. Metabolomics: From Fundamentals to Clinical Applications. Cham: Springer International Publishing; 2017. p. 99-141.
[52] Morbioli GG, Mazzu-Nascimento T, Aquino A, Cervantes C, Carrilho E. Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review. Analytica Chimica Acta. 2016;935(Supplement C):44-57.
[53] Ranjbar L, Talebi M, Haddad PR, Park SH, Cabot JM, Zhang M, et al. In Silico Screening of TwoDimensional Separation Selectivity for Ion Chromatography × Capillary Electrophoresis Separation of Low-Molecular-Mass Organic Acids. Analytical Chemistry. 2017;89(17):8808-15.
[54] Wakayama M, Hirayama A, Soga T. Capillary Electrophoresis-Mass Spectrometry. In: Bjerrum JT, editor. Metabonomics: Methods and Protocols. New York, NY: Springer New York; 2015. p. 113-22.
[55] Zeng J, Yin P, Tan Y, Dong L, Hu C, Huang Q, et al. Metabolomics Study of Hepatocellular Carcinoma: Discovery and Validation of Serum Potential Biomarkers by Using Capillary Electrophoresis–Mass Spectrometry. Journal of Proteome Research. 2014;13(7):3420-31.
[56] Simionato AVC, Carrilho E, Tavares MFM. CE-MS and related techniques as a valuable tool in tumor biomarkers research. Proteomics – Clinical Applications. 2010;4(8-9):778-.
[57] Shyti R, Kohler I, Schoenmaker B, Derks RJE, Ferrari MD, Tolner EA, et al. Plasma metabolic profiling after cortical spreading depression in a transgenic mouse model of hemiplegic migraine by capillary electrophoresis – mass spectrometry. Molecular BioSystems. 2015;11(5):1462-71.
[58] Soga T, Baran R, Suematsu M, Ueno Y, Ikeda S, Sakurakawa T, et al. Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. Journal of Biological Chemistry. 2006;281(24):16768-76.
[59] Vernocchi P, Del Chierico F, Putignani L. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health. Frontiers in Microbiology. 2016;7:1144.
[60] Herrero M, Simó C, García-Cañas V, Ibáñez E, Cifuentes A. Foodomics: MS-based strategies in modern food science and nutrition. Mass Spectrometry Reviews. 2012;31(1):49-69.
[61] Alberch J, Barbosa J, Benavente F, Ginés S, Jaumot J, Pont L, et al. Metabolic profiling for the identification of Huntington biomarkers by on-line solid-phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools. 2016.
[62] Harada S, Takebayashi T, Kurihara A, Akiyama M, Suzuki A, Hatakeyama Y, et al. Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in communitydwelling men. Environmental Health and Preventive Medicine. 2016;21(1):18-26.
[63] González-Peña D, Dudzik D, Colina-Coca C, de Ancos B, García A, Barbas C, et al. Evaluation of onion as a functional ingredient in the prevention of metabolic impairments associated to diet-induced hypercholesterolaemia using a multiplatform approach based on LC-MS, CE-MS and GC-MS. Journal of Functional Foods. 2015;19(Part A):363-75.
[64] González-Peña D, Dudzik D, Colina-Coca C, de Ancos B, García A, Barbas C, et al. Multiplatform metabolomic fingerprinting as a tool for understanding hypercholesterolemia in Wistar rats. European Journal of Nutrition. 2016;55(3):997-1010.
[65] Mastrangelo A, Martos-Moreno GÁ, García A, Barrios V, Rupérez FJ, Chowen JA, et al. Insulin resistance in prepubertal obese children correlates with sex-dependent early onset metabolomic alterations. International Journal of Obesity (2005). 2016;40(10):1494-502.
[66] Naz S, Calderón ÁA, García A, Gallafrio J, Mestre RT, González EG, et al. Unveiling differences between patients with acute coronary syndrome with and without ST elevation through fingerprinting with CE-MS and HILIC-MS targeted analysis. E Electrophoresis. 2015;36(18):2303-13.
[67] González-Domínguez R, García A, García-Barrera T, Barbas C, Gómez-Ariza JL. Metabolomic profiling of serum in the progression of Alzheimer’s disease by capillary electrophoresis–mass spectrometry. ELECTROPHORESIS. 2014;35(23):3321-30.
[68] Ishikawa S, Sugimoto M, Kitabatake K, Sugano A, Nakamura M, Kaneko M, et al. Identification of salivary metabolomic biomarkers for oral cancer screening. Scientific Reports. 2016;6:31520.
[69] Yamamoto M, Ly R, Gill B, Zhu Y, Moran-Mirabal J, Britz-McKibbin P. Robust and High-Throughput Method for Anionic Metabolite Profiling: Preventing Polyimide Aminolysis and Capillary Breakages under Alkaline Conditions in Capillary Electrophoresis-Mass Spectrometry. Analytical Chemistry. 2016;88(21):10710-9.
[70] Kim Y, Lee I-S, Kim K-H, Park J, Lee J-H, Bang E, et al. Metabolic Profiling of Liver Tissue in Diabetic Mice Treated with Artemisia Capillaris and Alisma Rhizome Using LC-MS and CE-MS. The American journal of Chinese medicine. 2016;44(08):1639-61.
[71] Ibáñez C, Simó C, Martín-Álvarez PJ, Kivipelto M, Winblad B, Cedazo-Mínguez A, et al. Toward a Predictive Model of Alzheimer’s Disease Progression Using Capillary Electrophoresis–Mass Spectrometry Metabolomics. Analytical Chemistry. 2012;84(20):8532-40.
[72] Matsumoto M, Kibe R, Ooga T, Aiba Y, Kurihara S, Sawaki E, et al. Impact of Intestinal Microbiota on Intestinal Luminal Metabolome. Scientific Reports. 2012;2:233.
[73] Macedo AN, Mathiaparanam S, Brick L, Keenan K, Gonska T, Pedder L, et al. The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport. ACS Central Science. 2017;3(8):904-13.
[74] Saito N, Robert M, Kochi H, Matsuo G, Kakazu Y, Soga T, et al. Metabolite Profiling Reveals YihU as a Novel Hydroxybutyrate Dehydrogenase for Alternative Succinic Semialdehyde Metabolism in Escherichia coli. The Journal of Biological Chemistry. 2009;284(24):16442-51.
[75] Zhao Y, Zhao J, Zhao C, Zhou H, Li Y, Zhang J, et al. A metabolomics study delineating geographical location-associated primary metabolic changes in the leaves of growing tobacco plants by GC-MS and CE-MS. Scientific Reports. 2015;5:16346.
[76] Sato D, Akashi H, Sugimoto M, Tomita M, Soga T. Metabolomic profiling of the response of susceptible and resistant soybean strains to foxglove aphid, Aulacorthum solani Kaltenbach. Journal of Chromatography B. 2013;925(Supplement C):95-103.
[77] Levandi T, Leon C, Kaljurand M, Garcia-Cañas V, Cifuentes A. Capillary Electrophoresis Time-ofFlight Mass Spectrometry for Comparative Metabolomics of Transgenic versus Conventional Maize. Analytical Chemistry. 2008;80(16):6329-35.
[78] Iino K, Sugimoto M, Soga T, Tomita M. Profiling of the charged metabolites of traditional herbal medicines using capillary electrophoresis time-of-flight mass spectrometry. Metabolomics. 2012;8(1):99-108.
[79] Sugimoto M, Kaneko M, Onuma H, Sakaguchi Y, Mori M, Abe S, et al. Changes in the Charged Metabolite and Sugar Profiles of Pasteurized and Unpasteurized Japanese Sake with Storage. Journal of Agricultural and Food Chemistry. 2012;60(10):2586-93.
[80] Wang Y, Feng R, Wang R, Yang F, Li P, Wan J-B. Enhanced MS/MS coverage for metabolite identification in LC-MS-based untargeted metabolomics by target-directed data dependent acquisition with timestaggered precursor ion list. Analytica Chimica Acta. 2017;992(Supplement C):67-75.
[81] Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research. 2000;28(1):27-30. 24
[82] Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, et al. HMDB 3.0—The Human Metabolome Database in 2013. Nucleic Acids Research. 2013;41(Database issue):D801-D7.
[83] Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, et al. METLIN: a metabolite mass spectral database. Therapeutic drug monitoring. 2005;27(6):747-51.
[84] Sud M, Fahy E, Cotter D, Brown A, Dennis EA, Glass CK, et al. LMSD: LIPID MAPS structure database. Nucleic Acids Research. 2007;35(Database issue):D527-D32.
[85] Hirayama A, Sugimoto M, Suzuki A, Hatakeyama Y, Enomoto A, Harada S, et al. Effects of processing and storage conditions on charged metabolomic profiles in blood. Electrophoresis. 2015;36(18):2148- 55.
[86] Hirayama A, Wakayama M, Soga T. Metabolome analysis based on capillary electrophoresis-mass spectrometry. TrAC Trends in Analytical Chemistry. 2014;61(Supplement C):215-22.
[87] Sugimoto M, Hirayama A, Ishikawa T, Robert M, Baran R, Uehara K, Kawai K, Soga T, Tomita M. Differential metabolomics software for capillary electrophoresis-mass spectrometry data analysis. Metabolomics. 2010, 6(1):27–41.