http://dx.doi.org/10.4322/sc.2016.034

Multidimensional chromatographic techniques on the investigation of secondary metabolites

Prata, Paloma Santana; Mogollón, Noroska Gabriela Salazar; Augusto, Fabio

Palavras-chave: GCxGC, Multidimensional Techniques, Secondary Metabolites.

Resumo: Secondary metabolites may be defined as the compounds who are not involved with the growth and development of organisms, but they are but they are essential for the survival and continuity of the species. Because of their great structural diversity (alkaloids, terpenoids, glycosides, phenols, polyketides, the synthesis of fatty acid products, peptides) and the high degree of difficulty of analysis (complex matrices), the advancing of instrumentation machines for the analysis of secondary metabolites is required. In recent decades, non-comprehensive multidimensional techniques as LC/MS, CE/MS e GC/MS and comprehensive multidimensional techniques as LCxLC e GCxGC can be considerate one of the most utilized for secondary metabolites analysis. Thus, this review reports different types of multidimensional techniques (emphasis in comprehensive two-dimensional gas chromatography) for secondary metabolites studies and discusses its advantages and limitations.

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Referências Bibliográficas

[1] Fenie AR, Schauer N. Metabolomics-assisted breeding: a viable option for crop improvement?. TIG 2008; 25(1): 39-48.

[2] Kossel A. Ueber die chemische Zusammensetzung der Zelle. Arch Anat Physiol 1891: 181-186.

[3] Hadacek F. Secondary Metabolites as Plant Traits: Current Assessment and Future Perspectives. CRC Crit Rev Plant Sci 2002 21(4): 273–322.

[4] Chen F, Liu CJ; Tschaplinski TJ, Zhao N. Genomics of Secondary Matabolism in Populus: Interactions with Biotic and Abiotic Environments. CRC Crit Rev Plant Sci 2009 28(5): 375-392.

[5] Simões, CMO, Schenkel EP, Gosman G, Mello JCP, Mentz LA, Petrovick PR; Farmacognosia: da planta ao medicamento. 3° Edição. Florianópolis: Editora da UFSC; 2007.

[6] Andrae-Marobela K, Ghislain FW, Okatch H, Majinda RRT. Polyphenols: a diverse class of multi-target anti-HIV-1 agents. Curr Drug Metab 2012 14(4): 392-413.

[7] Carazolli LH, Zanatta L, Alberton EH, Figueiredo MSRB, Folador P, Damazio RG, Pizzolati MG, Silva FRMB. Flavanoids: Prospective Drug Candidates. Mini Rev Med Chem 2008 8(13): 1429-1440.

[8] Jananie RK, Priya V, Vijayalakshmi K. Secondary metabolites of Cynodon dactylon as an antagonist to angiotensin II type 1 receptor: Novel in silico drug targeting approach for diabetic retinopathy. J Pharmacol Pharmacother 2012 3(1): 20-25.

[9] Zhao N, Wang G, Norris A, Chen X, Chen F. Studying Plant Secondary Metabolism in the Age of Genomics.CRC Crit Rev Plant Sci 2013 32(6): 369-382.

[10] Humston E M, Dombek K M, Tu BP, Young ET, Synovec RE. Toward a global analysis of metabolites in regulatory mutants of yeast. Anal Bioanal Chem 2011 401: 2387-2402.

[11] Phillips JB, Beens J. Comprehensive two-dimensional gas chromatography: a hyphenated method with strong coupling between the two dimensions. J Chromatogr A 1999 856: 331-347.

[12] Marriot P, Shellie R. Principles and applications of comprehensive two-dimensional gas chromatography. Tr Anal Chem 2002 21:573-583.

[13] Giddings JC. Two-Dimensional Separations: Concept and Promise. Anal Chem 1984 56(12): 1258-1270.

[14] Edwards M, Mostafa A, Górecki T. Modulation in comprehensive two-dimentional gas chromatography: 20 years of innovation. Anal Bioanal Chem 2011 401: 2335-2349.

[15] Marriott PJ, Chin ST, Maikhunthod B, Schmarr HG, Bieri S. Multidimensional gas Chromatography. TrAC Trends Anal Chem 2012 34: 1-21.

[16] Patti GJ, Tautenhahn R, Rinehart D, Cho K, Shriver LP, Manchester M, Nikolskiy I, Johonson CH, Mahieu NG, Siuzdak G. Metabolomics: the apogee of the omics trilogy. Anal Chem 2012 85: 798-804.

[17] Gomathi D, Kalaiselvi M, Ravikumar G, Devaki K, Uma C. GC-MS analysis of bioactive compounds from the whole plant ethanolic extract of Evolvulus alsinoides (L.) L. J Food Sci Technol 2013 22: 1155-1161.

[18] Kim JK, Park SY, Lim SH, Yeo Y, Cho HS, Ha SH. Comparative metabolic profiling of pigmented rice (Oryza sativa L.) cultivars reveals primary metabolites are correlated with secondary metabolites. J Cereal Sci 2013 57: 14-20.

[19] Collins CH, Braga GL, Bonato PS; Fundamentos de Cromatografia. Campinas: Editora da UNICAMP; 2006.

[20] Allwood JW, Goodacre R. An introduction to liquid chromatography–mass spectrometry instrumentation applied in plant metabolomic analyses. Phytochem Anal 2010 21: 33-47.

[21] Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989 246: 64-71.

[22] University of Bristol [homepage na internet]. High Performance Liquid Chromatography Mass Spectrometry (HPLC/MS)/ Eletrospray Ionisation [acesso em 25 set 2015]. Disponível em : http://www.bris.ac.uk/nerclsmsf/techniques/hplcms.html

[23] Nakabayashi R, Saito K. Metabolomics for unknown plant metabolites. Anal Bioanal Chem 2013 405(15): 5005-5011.

[24] Wojakowska A, Piasecka A, Gacía-López PM, Zamora-Natera F, Krajewski P, Marczak L, Kachlicki P, Stobiecki M. Structural analysis and profiling of phenolic secondary metabolites of Mexican lupine species using LC–MS techniques. Phytochemistry 2013 92: 71-86.

[25] Aquino Neto FR, Nunes DSS; Cromatografia: Princípios básicos e técnicas afins. Rio de Janeiro: Interciência; 2003.

[26] Unger M. Capillary Electrophoresis of Natural Products: Current Applications and Recent Advances. Planta Med 2009 75: 735- 745.

[27] Saric J, Want EJ, Duthaler U, Lewis M, Keiser J, Shockcor JP, Ross GA, Nicholson JK, Holmes E, Tavares MFM. Systematic Evaluation of Extraction Methods for Multiplatform-Based Metabotyping: Application to the Fasciola hepatica Metabolome. Anal Chem 2012 84(16): 6963-6972.

[28] Contreras-Gutiérrez PK, Hurtado-Fernández E, Gómez-Romero M, Hormaza JI, Carrasco-Pancorbo A, Férnandez-Gutiérrez A. Determination of changes in the metabolic profile of avocado fruits (Persea americana) by two CE-MS approaches (targeted and non-targeted). Electrophoresis 2013. 34: 2928-2942.

[29] Herrero M, Garcia-Canas V, Simo C, Cifuentes A. Recent advances in the application of capillary electromigration methods for food analysis and Foodomics. Electrophoresis 2010 31: 205-228.

[30] Seeley JV. Recent advances in flow-controlled multidimensional gas chromatography. J Chromatogr A 2012 1255: 24-37.

[31] Giddings JC. Maximum Number of Components Resolvable by Gel Filtration and Other Elution Chromatographic Methods. Anal Chem 1967 39 1027-1028.

[32] Bertsch W. Two-Dimensional Gas Chromatography. Concepts, Instrumentation, and Applications – Part 1: Fundamentals, Conventional Two-Dimensional Gas Chromatography, Selected Applications. J High Resolut Chromatogr 1999 22(12): 647-665.

[33] Gras R, Loung J, Hawryluk M, Monagle M. Analysis of part-per-billion level of arsine and phosphine in light hydrocarbons by capillary flow technology and dielectric barrier discharge detector. J Chromatogr A 2010 1217: 348-352.

[34] Su YC, Liu WT, Liao WC, Chiang SW, Wang JL. Full-range analysis of ambient volatile organic compounds by a new trapping method and gas chromatography/mass spectrometry. J Chromatogr A 2011 1218: 5733-5742.

[35] Ma Y, Hays MD, Geron CD, Walker JT, Gichuru MJG. Technical Note: Fast two-dimensional GC-MS with thermal extraction for anhydro-sugars in fine aerosols. Atmos Chem Phys 2010 10: 4331-4341.

[36] Cunha SC, Fernandes JO. Quantification of free and total bisphenol A and bisphenol B in human urine by dispersive liquid–liquid microextraction (DLLME) and heart-cutting multidimensional gas chromatography–mass spectrometry (MD–GC/MS). Talanta 2010 83: 117-125.

[37] David F, Jacq K, Sandra P, Baker A, Klee MS. Analyses of potential genotoxic impurities by two-dimensional gas chromatography with Deans switching and independent column temperature control using a low-thermal-mass oven module. Anal Bioanal Chem 2010 396: 1291-1300.

[38] Ren Q, Wu C, Zhang J. Use of on-line stop-flow heart-cutting two-dimensional high performance liquid chromatography for simultaneous determination of 12 major constituents in tartary buckwheat (Fagopyrum tataricum Gaertn). J Chomatogr A 2013 1304: 257-262.

[39] Ciésla L, Waksmundzka-Hajnos M. Two-dimensional thin-layer chromatography in the analysis of secondary plant metabolites. J Chomatogr A 2009 1216: 1035-1052.

[40] D’Attoma A, Grivel C, Heinisch S. On-line comprehensive two-dimensional separations of charged compounds using reversedphase high performance liquid chromatography and hydrophilic interaction chromatography. Part I: Orthogonality and practical peak capacity considerations. J Chomatogr A 2012 1262: 148-159.

[41] Scoemnmakers PJ, Marriott P, Beens J. Nomenclature and conventions in comprehensive multidimensional chromatography. LC-GC Europe 2003 16: 335-339.

[42] Purcaro P, Moret S, Conte L. Hyphenated liquid chromatography–gas chromatography technique: Recent evolution and applications. J Chomatogr A 2012 1255: 100-111.

[43] Purcaro P, Moret S, Conte L. Sample pre-fractionation of environmental and food samples using LC-GC multidimensional techniques. TrAC Trends Anal Chem 2013 43: 146-170.

[44] Liu Z, Phillips JB. Comprehensive Two-Dimensional Gas Chromatography using an On-Column Thermal Modulator Interface. J Chromatogr Sci 1991 29: 227.

[45] Murray JA. Qualitative and quantitative approaches in comprehensive two-dimensional gas chromatography. J Chomatogr A 2012 1261: 58-68.

[46] Giddings JC. Sample dimensionality: a predictor of order-disorder in component peak distribution in multidimensional separation. J Chomatogr A 1995 703: 3-15.

[47] Almstetter MF, Appel IJ, Dettmer K, Gruber MA, Oefner PJ. Comparison of two algorithmic data processing strategies for metabolic fingerprinting by comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry. J Chomatogr A 2011 1218: 7031-7038.

[48] Marriott P, Shellie R. Principles and applications of comprehensive two-dimensional gas chromatography. Trend Anal Chem 2002 21: 573-583.

[49] Rian D; Morrison P, Marriott P. Orthogonality considerations in comprehensive two-dimensional gas chromatography. J Chomatogr A 2005 1071: 47-53.

[50] Mondello L; Comprehensive Chromatography in Combination with Mass Spectrometry. New Jersey: Wiley; 2011.

[51] Harynuk J, Marriott P. Comprehensive multidimensional separations. Anal Bioanal Chem 2011 401: 2333-2334.

[52] Mostafa A, Edwards M, Górecki T. Optimization aspects of comprehensive two-dimensional gas chromatography J Chomatogr A 2012 1255: 38-55.

[53] Murphy RE, Schure MR, Foley JP. Effect of Sampling Rate on Resolution in Comprehensive Two-Dimensional Liquid Chromatography. Anal Chem 1998 70: 1585-1594.

[54] Seeley JV, Seeley SK. Multidimensional Gas Chromatography: Fundamental Advances and New Applications. Anal Chem 2013 85(2): 557-578.

[55] Tranchida PQ, Franchina FA, Zoccali M, Pantó S, Sciarrone D, Dugo P, Mondello L. Untargeted and targeted comprehensive two-dimensional GC analysis using a novel unified high-speed triple quadrupole mass spectrometer. J Chomatogr A 2013 1278: 153-159.

[56] Ragonese C, Sciarrone D, Tranchida PQ, Dugo P, Mondello L. Use of ionic liquids as stationary phases in hyphenated gas chromatography techniques. J Chomatogr A 2012 1255: 130-144.

[57] Nosheen A, Mitrevski B, Bano A, Marriott PJ. Fast Comprehensive Two-Dimensional Gas Chromatography Method for Fatty Acid Methyl Ester Separation and Quantification Using DUAL Ionic Liquid Columns. J Chomatogr A 2013 1312: 118-123.

[58] Zeng AX, Chin ST, Nolvachai Y, Kulsing C, Sidisky LM, Marriott PJ. Characterisation of capillary ionic liquid columns for gaschromatography–mass spectrometry analysis of fatty acid methylesters. Anal Chim Acta 2013 803: 166-173.

[59] Peroni D, Vonk RJ, Egmond W, Janssen HG. Macroporous polymer monoliths as second dimension columns in comprehensive two-dimensional gas chromatography: A feasibility study. J Chomatogr A 2012 1268: 139-149.

[60] Seeley JV, Kramp FJ, Sharpe KS. A dual-secondary column comprehensive two-dimensional gas chromatograph for the analysis of volatile organic compound mixtures. J Sep Sci 2001 24: 444-450.

[61] Seeley JV, Kramp FJ, Sharpe KS, Seeley KS. Characterization of gaseous mixtures of organic compounds with dual-secondary column comprehensive two-dimensional gas chromatography. J Sep Sci 2002 25: 53-59.

[62] Savareear B, Shellie RA. Multiplexed dual second-dimension column comprehensivetwo-dimensional gas chromatography (GC × 2GC) using thermal modulation and contra-directional second-dimension columns. Anal Chim Acta 2013 803: 160-165.

[63] Peroni D, Sampat AAS, Egmond W, Koning S, Cochran J, Lautamo R, Jassen HG. Comprehensive two-dimensional gas chromatography with a multi-capillary second dimension: A new column-set format forsimultaneous optimum linear velocity operation. J Chomatogr A 2013 1317: 3-11.

[64] Dallüge J, Beens J, Brinkman UAT. Comprehensive two-dimensional gas chromatography: a powerful and versatile analytical tool. J Chomatogr A 2003 1000: 69-108.

[65] Liu Z, Phillips JB. Comprehensive Two-Dimensional Gas Chromatography using an On-Column Thermal Modulator Interface. J Chomatogr Sci 1991 29: 227-231.

[66] Bruckner CA, Prazen BJ, Synovec RE. Comprehensive Two-Dimensional High-Speed Gas Chromatography with Chemometric Analysis. Anal Chem 1998 70: 2796-2804.

[67] Kinghorn RM, Marriott PJ. Comprehensive Two-Dimensional High-Speed Gas Chromatography with Chemometric Analysis. Journal High Resolut Chromatogr 2000 23(3): 245-252.

[68] Beens J, Adahchour M, Vreuls RJJ, Altena K, Brinkman U. Simple, non-moving modulation interface for comprehensive twodimensional gas chromatography. J Chomatogr A 2001 919: 127-132.

[69] Bueno PA, Seeley JV. Flow-switching device for comprehensive two-dimensional gas chromatography. J Chomatogr A 2004 1027: 3-10.

[70] Diehl JW, Sanzo FP. Determination of aromatic hydrocarbons in gasolines by flow modulated comprehensive two-dimensional gas chromatography. J Chomatogr A 2005 1080: 157-165.

[71] Seeley JV, Micyus NJ, McCurry JD, Seeley SK. Comprehensive Two-Dimensional Gas Chromatography With a Simple Fluidic Modulator. Am Lab News 2006 38: 24-26.

[72] Poliack M, Kochman M, Amirav A. Pulsed flow modulation comprehensive two-dimensional gas chromatography. J Chomatogr A 2008 1186: 189-195.

[73] Harynuk J, Górecki T. Comparison of comprehensive two-dimensional gas chromatography in conventional and stop-flow modes. J Chomatogr A 2006 1105: 159-167.

[74] Seeley JV, Micyus NJ, Bandurski SV, Seeley SK, McDCurry J. Microfluidic Deans Switch for Comprehensive Two-Dimensional Gas Chromatography. Anal Chem 2007 79(5): 573-583.

[75] Tranchida PQ, Purcaro G, Visco A, Conte L, Dugo P, Dawes P, Mondello L. A flexible loop-type flow modulator for comprehensive two-dimensional gas chromatography. J Chomatogr A 2011 1218: 3140-3145.

[76] Griffith JF, Winniford WL, Sun K, Edam R, Luong JC. A reversed-flow differential flow modulator for comprehensive twodimensional gas chromatography. J Chomatogr A 2012 1226: 116-123.

[77] Lidster RT, Hamilton JF, Lewis AC. The application of two total transfer valve modulators for comprehensive twodimensional gas chromatography of volatile organic compounds. J Separat Sci 2011 34: 812-821.

[78] Kinghorn RM, Marriott PJ. Comprehensive Two-Dimensional Gas Chromatography Using a Modulating Cryogenic Trap. J High Resolut Chromatogra 1998 21(11): 620-622.

[79] Gaines RB, Frysinger GS. Temperature requirements for thermal modulation in comprehensive two-dimensional gas chromatography. J Sep Sci 2004 27: 380-388.

[80] Semard G, Gouin C, Bourdet J, Bord N, Livadaris V. Comparative study of differential flow and cryogenic modulators comprehensive two-dimensional gas chromatography systems for the detailed analysis of light cycle oil. J Chomatogr A 2011 1218: 3146-3152.

[81] Hantao LW, Aleme HG, Passador MM, Furtado EL, Ribeiro FAL, Poppi RJ, Augusto F. Determination of disease biomarkers in Eucalyptus by comprehensive two-dimensional gas chromatography and multivariate data analysis. J Chomatogr A 2013a. 1279: 86-91.

[82] Hantao LW, Toledo BR, Ribeiro FAL, Pizetta M, Pierozzi CG, Furtado EL, Augusto F. Comprehensive two-dimensional gas 1 chromatography combined to multivariate data 2 analysis for the detection of disease-resistant clones 3 of Eucalyptus. Talanta 2013 116: 1079-1084.

[83] Timischl B, Dettmer K, Kaspar H, Thieme M, Oefner PJ. Development of a quantitative validated capillary electrophoresis-time of flight-mass spectrometry method with integrated high-confidence analyte identification of metabolomics. Electrophoresis 2008 29: 2203-2214.

[84] Cai H, Cao G, Li L, Liu X, Ma XQ, Tu SC, Lou YJ, Qin KM, Li SL, Ca BC. Profiling and Characterization of Volatile Components from Non-Fumigated and Sulfur-Fumigated Flos Lonicerae Japonicae Using Comprehensive Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry Coupled with Chemical Group Separation. Molecules 2013 18: 1368-1382.

[85] Rahman A, Kang SC. In vitro control of food-borne and food spoilage bacteria by essential oil and ethanol extracts of Lonicera japonica Thunb. Food Chem 2009 116: 670-675.

[86] Feng Q, Ren Y, Wang Y, Ma H, Xu J, Zhou CR, Yin C, Luo L. Anti-inflammatory effect of SQC-β-CD on lipopolysaccharideinduced acute lung injury. J Ethnopharmacol 2008 118: 51-58.

[87] Chang CW, Lin MT, Lee SS, Liu KCSC, Hsu FL, Lin JY. Differential inhibition of reverse transcriptase and cellular DNA polymerase-α activities by lignans isolated from Chinese herbs, Phyllanthus myrtifolius Moon, and tannins from Lonicera japonica Thunb and Castanopsis hystrix. Antiviral Res 1995 27: 367-374.

[88] Cao G, Shan Q, Li X, Cong X, Zhang Y, Cai H, Cai B. Analysis of fresh Mentha haplocalyx volatile components by comprehensive two-dimensional gas chromatography and high-resolution time-of-flight mass spectrometry. Analyst 2011 136: 4653-4661.

[89] Zhao D, Xu YW, Yang GL, Husainib AM, Wu W. Variation of essential oil of Mentha haplocalyx Briq. and Mentha spicata L. from China. Ind Crops Prod 2013 42: 251-260.

[90] Erni F, Frei W. Two-Dimensional column liquid chromatographic technique for resolution of complex mixtures. J Chomatogr 1978 149: 561-569.

[91] Jeonga EK, Chaa HJ, Hac YW, Kimd YS, Had IJ, Na YC. Development and optimization of a method for the separation of platycosides in Platycodi Radix by comprehensive two-dimensional liquid chromatography with mass spectrometric detection. J Chomatogr A 2010 1217: 4375-4382.