Mass spectrometry-based metabolomics.

This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very diverse physico-chemical properties and occur at different abundance levels. Consequently, comprehensive metabolomics investigations are primarily a challenge for analytical chemistry and specifically mass spectrometry has vast potential as a tool for this type of investigation. Metabolomics require special approaches for sample preparation, separation, and mass spectrometric analysis. Current examples of those approaches are described in this review. It primarily focuses on metabolic fingerprinting, a technique that analyzes all detectable analytes in a given sample with subsequent classification of samples and identification of differentially expressed metabolites, which define the sample classes. To perform this complex task, data analysis tools, metabolite libraries, and databases are required. Therefore, recent advances in metabolomics bioinformatics are also discussed.

[1]  A. Clifford,et al.  Absorption and retinol equivalence of beta-carotene in humans is influenced by dietary vitamin A intake. , 2003, Journal of lipid research.

[2]  Andrew Hayes,et al.  An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. , 2003, Phytochemistry.

[3]  I. Wilson,et al.  A metabonomic investigation of the biochemical effects of mercuric chloride in the rat using 1H NMR and HPLC-TOF/MS: time dependent changes in the urinary profile of endogenous metabolites as a result of nephrotoxicity. , 2004, The Analyst.

[4]  M. Balazy.  Eicosanomics: targeted lipidomics of eicosanoids in biological systems. , 2004, Prostaglandins & other lipid mediators.

[5]  I. Wilson,et al.  High resolution "ultra performance" liquid chromatography coupled to oa-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies. , 2005, Journal of proteome research.

[6]  J. Bruce German,et al.  Lipid metabolome-wide effects of the PPARγ agonist rosiglitazones⃞s The online version of this article (available at http://www.jlr.org) contains an additional 4 tables. Published, JLR Papers in Press, August 16, 2002. DOI 10.1194/jlr.M200169-JLR200 , 2002, Journal of Lipid Research.

[7]  Masaru Tomita,et al.  Simultaneous determination of the main metabolites in rice leaves using capillary electrophoresis mass spectrometry and capillary electrophoresis diode array detection. , 2004, The Plant journal : for cell and molecular biology.

[8]  R. Takors,et al.  Metabolomics: quantification of intracellular metabolite dynamics. , 2002, Biomolecular engineering.

[9]  R. DuBois,et al.  Targeted lipidomics using electron capture atmospheric pressure chemical ionization mass spectrometry. , 2003, Rapid communications in mass spectrometry : RCM.

[10]  J. Frisvad,et al.  Terverticillate penicillia studied by direct electrospray mass spectrometric profiling of crude extracts. I. Chemosystematics , 1997 .

[11]  Oliver Fiehn,et al.  Analysis of highly polar compounds of plant origin: combination of hydrophilic interaction chromatography and electrospray ion trap mass spectrometry. , 2002, Analytical biochemistry.

[12]  W. Griffiths.  Tandem mass spectrometry in the study of fatty acids, bile acids, and steroids. , 2003, Mass spectrometry reviews.

[13]  S. Catinella,et al.  Different electrospray tandem mass spectrometric approaches for rapid characterization of phospholipid classes of Curosurf, a natural pulmonary surfactant. , 2002, Rapid communications in mass spectrometry : RCM.

[14]  G. Kruppa,et al.  Metabolomics applications of FT-ICR mass spectrometry. , 2005, Mass spectrometry reviews.

[15]  M. Barcelona,et al.  Structural determination and quantitative analysis of bacterial phospholipids using liquid chromatography/electrospray ionization/mass spectrometry , 1998 .

[16]  R. Murphy,et al.  Electrospray mass spectrometry of phospholipids. , 2003, Mass spectrometry reviews.

[17]  H. Maibach,et al.  HPLC-accelerator MS measurement of atrazine metabolites in human urine after dermal exposure. , 1999, Analytical chemistry.

[18]  Chris F. Taylor,et al.  A common open representation of mass spectrometry data and its application to proteomics research , 2004, Nature Biotechnology.

[19]  I. Wilson,et al.  D-Serine-induced nephrotoxicity: a HPLC-TOF/MS-based metabonomics approach. , 2005, Toxicology.

[20]  Ian D Wilson,et al.  Metabonomic analysis of mouse urine by liquid-chromatography-time of flight mass spectrometry (LC-TOFMS): detection of strain, diurnal and gender differences. , 2003, The Analyst.

[21]  R. Bino,et al.  The light-hyperresponsive high pigment-2dg mutation of tomato: alterations in the fruit metabolome. , 2005, The New phytologist.

[22]  C. Beecher,et al.  The Human Metabolome , 2003 .

[23]  W. Matson,et al.  Characterization of diet-dependent metabolic serotypes: analytical and biological variability issues in rats. , 2001, The Journal of nutrition.

[24]  Pedro Mendes,et al.  Emerging bioinformatics for the metabolome , 2002, Briefings Bioinform..

[25]  C. Wittmann,et al.  Application of MALDI-TOF MS to lysine-producing Corynebacterium glutamicum: a novel approach for metabolic flux analysis. , 2001, European journal of biochemistry.

[26]  D. Kell,et al.  High-throughput classification of yeast mutants for functional genomics using metabolic footprinting , 2003, Nature Biotechnology.

[27]  G. Mills,et al.  Headspace solid-phase microextraction procedures for gas chromatographic analysis of biological fluids and materials. , 2000, Journal of chromatography. A.

[28]  J. Smedsgaard.  Micro-scale extraction procedure for standardized screening of fungal metabolite production in cultures. , 1997, Journal of chromatography. A.

[29]  Douglas B. Kell,et al.  High-Throughput Metabolic Fingerprinting of Legume Silage Fermentations via Fourier Transform Infrared Spectroscopy and Chemometrics , 2004, Applied and Environmental Microbiology.

[30]  Age K. Smilde,et al.  ANOVA-simultaneous component analysis (ASCA): a new tool for analyzing designed metabolomics data , 2005, Bioinform..

[31]  Jonathan L Josephs,et al.  Creation and comparison of MS/MS spectral libraries using quadrupole ion trap and triple-quadrupole mass spectrometers. , 2004, Rapid communications in mass spectrometry : RCM.

[32]  A. Hoffmann,et al.  Analysis of volatile organic compounds in human urine by headspace gas chromatography-mass spectrometry with a multipurpose sampler. , 1999, Journal of chromatography. A.

[33]  K. Dettmer,et al.  Studies of thermally assisted hydrolysis and methylation-GC-MS of fatty acids and triglycerides using different reagents and injection systems , 2003 .

[34]  Ian D Wilson,et al.  HPLC-MS-based methods for the study of metabonomics. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[35]  A. Merrill,et al.  Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. , 2005, Methods.

[36]  E. Stashenko,et al.  Analysis of volatile secondary metabolites from Colombian Xylopia aromatica (Lamarck) by different extraction and headspace methods and gas chromatography. , 2004, Journal of chromatography. A.

[37]  James L. Little,et al.  Artifacts in trimethylsilyl derivatization reactions and ways to avoid them. , 1999, Journal of chromatography. A.

[38]  Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems. , 2001, The Plant cell.

[39]  B. Hammock,et al.  Soluble epoxide hydrolase is a therapeutic target for acute inflammation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J Bruce German,et al.  Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone. , 2002, Journal of lipid research.

[41]  P. Isakson,et al.  Rapid quantitation of a large scope of eicosanoids in two models of inflammation: development of an electrospray and tandem mass spectrometry method and application to biological studies. , 1996, Analytical Biochemistry.

[42]  M. Reuss,et al.  In vivo analysis of glucose-induced fast changes in yeast adenine nucleotide pool applying a rapid sampling technique. , 1993, Analytical biochemistry.

[43]  B. Hammock,et al.  The simultaneous quantification of cytochrome P450 dependent linoleate and arachidonate metabolites in urine by HPLC-MS/MS DOI 10.1194/jlr.D200018-JLR200 , 2002, Journal of Lipid Research.

[44]  H. Schiebel,et al.  Structure elucidation of phase II metabolites by tandem mass spectrometry: an overview. , 2005, Journal of chromatography. A.

[45]  J. Nielsen,et al.  Global metabolite analysis of yeast: evaluation of sample preparation methods , 2005, Yeast.

[46]  Kazuki Saito,et al.  Potential of metabolomics as a functional genomics tool. , 2004, Trends in plant science.

[47]  I. Wilson,et al.  Cyclosporin A-induced changes in endogenous metabolites in rat urine: a metabonomic investigation using high field 1H NMR spectroscopy, HPLC-TOF/MS and chemometrics. , 2004, Journal of pharmaceutical and biomedical analysis.

[48]  C. Cannizzaro,et al.  Metabolic network analysis on Phaffia rhodozyma yeast using 13C-labeled glucose and gas chromatography-mass spectrometry. , 2004, Metabolic Engineering.

[49]  Somenath Mitra,et al.  Sample preparation techniques in analytical chemistry , 2003 .

[50]  J Bruce German,et al.  Toward the implementation of metabolomic assessments of human health and nutrition. , 2002, Current opinion in biotechnology.

[51]  I. Wilson,et al.  Understanding 'Global' Systems Biology: Metabonomics and the Continuum of Metabolism , 2003, Nature Reviews Drug Discovery.

[52]  Helena Idborg,et al.  Multivariate approaches for efficient detection of potential metabolites from liquid chromatography/mass spectrometry data. , 2004, Rapid communications in mass spectrometry : RCM.

[53]  Hans-Gerd Janssen,et al.  Method development in high-performance liquid chromatography for high-throughput profiling and metabonomic studies of biofluid samples. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[54]  Xianlin Han,et al.  Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. , 2003, Journal of lipid research.

[55]  O. Fiehn,et al.  Identification of uncommon plant metabolites based on calculation of elemental compositions using gas chromatography and quadrupole mass spectrometry. , 2000, Analytical chemistry.

[56]  Jonathan E Katz,et al.  A new technique (COMSPARI) to facilitate the identification of minor compounds in complex mixtures by GC/MS and LC/MS: tools for the visualization of matched datasets , 2004, Journal of the American Society for Mass Spectrometry.

[57]  Douglas B. Kell,et al.  Discrimination of Modes of Action of Antifungal Substances by Use of Metabolic Footprinting , 2004, Applied and Environmental Microbiology.

[58]  M. Udvardi,et al.  Global changes in transcription orchestrate metabolic differentiation during symbiotic nitrogen fixation in Lotus japonicus. , 2004, The Plant Journal.

[59]  U. Sauer.  High-throughput phenomics: experimental methods for mapping fluxomes. , 2004, Current opinion in biotechnology.

[60]  Mohamed Adahchour,et al.  Comprehensive two-dimensional gas chromatography coupled to a rapid-scanning quadrupole mass spectrometer: principles and applications. , 2005, Journal of chromatography. A.

[61]  J. Visser,et al.  Determination of intermediary metabolites in Aspergillus niger. , 1996 .

[62]  T. Ferenci,et al.  Global metabolite analysis: the influence of extraction methodology on metabolome profiles of Escherichia coli. , 2003, Analytical biochemistry.

[63]  Ute Roessner,et al.  Simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry. , 2000 .

[64]  D. Kell,et al.  Flow-injection electrospray ionization mass spectrometry of crude cell extracts for high-throughput bacterial identification , 2002, Journal of the American Society for Mass Spectrometry.

[65]  S. Lemire,et al.  Calibration Point for Liquid Secondary Ion MassSpectrometry Tandem Mass Spectra Measuredwith an EBqQ Hybrid Mass Spectrometer , 1996 .

[66]  M. Billeter,et al.  Automated peak picking and peak integration in macromolecular NMR spectra using AUTOPSY. , 1998, Journal of magnetic resonance.

[67]  D. Chace,et al.  The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. , 2002, Annual review of genomics and human genetics.

[68]  E. Vuori,et al.  Toxicological screening with formula-based metabolite identification by liquid chromatography/time-of-flight mass spectrometry. , 2003, Analytical chemistry.

[69]  John C. Lindon,et al.  Pattern recognition methods and applications in biomedical magnetic resonance , 2001 .

[70]  M. Sjöström,et al.  Design of experiments: an efficient strategy to identify factors influencing extraction and derivatization of Arabidopsis thaliana samples in metabolomic studies with gas chromatography/mass spectrometry. , 2004, Analytical biochemistry.

[71]  M. Tomita,et al.  Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. , 2003, Journal of proteome research.

[72]  Ina Schuppe-Koistinen,et al.  Screening of biomarkers in rat urine using LC/electrospray ionization-MS and two-way data analysis. , 2003, Analytical chemistry.

[73]  O. Fiehn,et al.  Process for the integrated extraction, identification and quantification of metabolites, proteins and RNA to reveal their co‐regulation in biochemical networks , 2004, Proteomics.

[74]  M. Viant.  Improved methods for the acquisition and interpretation of NMR metabolomic data. , 2003, Biochemical and biophysical research communications.

[75]  U. Roessner,et al.  Technical advance: simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry. , 2000, The Plant journal : for cell and molecular biology.

[76]  Mariusz Kowalczyk,et al.  A strategy for identifying differences in large series of metabolomic samples analyzed by GC/MS. , 2004, Analytical chemistry.

[77]  Joachim Selbig,et al.  Metabolite fingerprinting: detecting biological features by independent component analysis , 2004, Bioinform..

[78]  J J Heijnen,et al.  MIRACLE: mass isotopomer ratio analysis of U‐13C‐labeled extracts. A new method for accurate quantification of changes in concentrations of intracellular metabolites , 2004, Biotechnology and bioengineering.

[79]  J. Henion,et al.  Electrospray and tandem mass spectrometric characterization of acylglycerol mixtures that are dissolved in nonpolar solvents. , 1991, Analytical chemistry.

[80]  T. Hadfield,et al.  Direct mass spectrometric analysis of in situ thermally hydrolyzed and methylated lipids from whole bacterial cells. , 1998, Analytical chemistry.

[81]  Martin Lindner,et al.  Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. , 2003, Pediatrics.

[82]  Oliver Fiehn,et al.  Monolithic silica-based capillary reversed-phase liquid chromatography/electrospray mass spectrometry for plant metabolomics. , 2003, Analytical chemistry.

[83]  C. Wittmann,et al.  Impact of the cold shock phenomenon on quantification of intracellular metabolites in bacteria. , 2004, Analytical biochemistry.

[84]  Oliver Fiehn,et al.  Metabolic networks of Cucurbita maxima phloem. , 2003, Phytochemistry.

[85]  J. Kopka,et al.  Comprehensive chemical derivatization for gas chromatography-mass spectrometry-based multi-targeted profiling of the major phytohormones. , 2003, Journal of chromatography. A.

[86]  E. Stashenko,et al.  Comparison of different extraction methods for the analysis of volatile secondary metabolites of Lippia alba (Mill.) N.E. Brown, grown in Colombia, and evaluation of its in vitro antioxidant activity. , 2004, Journal of chromatography. A.

[87]  A. Saghatelian,et al.  Assignment of endogenous substrates to enzymes by global metabolite profiling. , 2004, Biochemistry.

[88]  Donald H Chace,et al.  A biochemical perspective on the use of tandem mass spectrometry for newborn screening and clinical testing. , 2005, Clinical biochemistry.

[89]  S. Yamaguchi,et al.  Simplified screening for organic acidemia using GC/MS and dried urine filter paper: a study on neonatal mass screening. , 2000, Early human development.

[90]  Yves Gibon,et al.  GMD@CSB.DB: the Golm Metabolome Database , 2005, Bioinform..

[91]  Christophe Junot,et al.  Metabolite profiling in rat urine by liquid chromatography/electrospray ion trap mass spectrometry. Application to the study of heavy metal toxicity. , 2003, Rapid communications in mass spectrometry : RCM.

[92]  A. Lubben,et al.  Reproducible product-ion tandem mass spectra on various liquid chromatography/mass spectrometry instruments for the development of spectral libraries. , 2004, Rapid communications in mass spectrometry : RCM.

[93]  F. Hsu,et al.  Structural characterization of triacylglycerols as lithiated adducts by electrospray ionization mass spectrometry using low-energy collisionally activated dissociation on a triple stage quadrupole instrument , 1999, Journal of the American Society for Mass Spectrometry.

[94]  Robert S Plumb,et al.  Metabonomics: the use of electrospray mass spectrometry coupled to reversed-phase liquid chromatography shows potential for the screening of rat urine in drug development. , 2002, Rapid communications in mass spectrometry : RCM.

[95]  S. Turner,et al.  Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. , 1997, The Journal of clinical investigation.

[96]  H. Brown,et al.  Computational lipidomics: a multiplexed analysis of dynamic changes in membrane lipid composition during signal transduction. , 2004, Molecular pharmacology.

[97]  R. Goodacre,et al.  Metabolic Profiling: Its Role in Biomarker Discovery and Gene Function Analysis , 2003, Springer US.

[98]  Stephen J. Bruce,et al.  Extraction, interpretation and validation of information for comparing samples in metabolic LC/MS data sets. , 2005, The Analyst.

[99]  David M. Rocke,et al.  Discrimination models using variance-stabilizing transformation of metabolomic NMR data. , 2004, Omics : a journal of integrative biology.

[100]  Xianlin Han,et al.  Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. , 2005, Mass spectrometry reviews.

[101]  Royston Goodacre,et al.  Application of high-throughput Fourier-transform infrared spectroscopy in toxicology studies: contribution to a study on the development of an animal model for idiosyncratic toxicity. , 2004, Toxicology letters.

[102]  Matej Oresic,et al.  MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data , 2006, Bioinform..

[103]  K. Brown,et al.  Techniques: the application of accelerator mass spectrometry to pharmacology and toxicology. , 2004, Trends in pharmacological sciences.

[104]  T. Kuhara.  Gas chromatographic-mass spectrometric urinary metabolome analysis to study mutations of inborn errors of metabolism. , 2005, Mass spectrometry reviews.

[105]  D. Marsden,et al.  Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. , 2001, Clinical chemistry.

[106]  W. Weckwerth.  Metabolomics in systems biology. , 2003, Annual review of plant biology.

[107]  O. Fiehn.  Metabolomics – the link between genotypes and phenotypes , 2004, Plant Molecular Biology.

[108]  J. Steghens,et al.  ESI-MS/MS analysis of underivatised amino acids: a new tool for the diagnosis of inherited disorders of amino acid metabolism. Fragmentation study of 79 molecules of biological interest in positive and negative ionisation mode. , 2003, Rapid communications in mass spectrometry : RCM.

[109]  Félix Hernández,et al.  Use of quadrupole time-of-flight mass spectrometry in the elucidation of unknown compounds present in environmental water. , 2005, Rapid communications in mass spectrometry : RCM.

[110]  J. Haselden,et al.  Use of liquid chromatography/time-of-flight mass spectrometry and multivariate statistical analysis shows promise for the detection of drug metabolites in biological fluids. , 2003, Rapid communications in mass spectrometry : RCM.

[111]  A. Snyder,et al.  Characterization of underivatized lipid biomarkers from microorganisms with pyrolysis short-column gas chromatography/ion trap mass spectrometry. , 1990, Analytical chemistry.

[112]  C. Wittmann,et al.  Metabolic flux analysis using mass spectrometry. , 2002, Advances in biochemical engineering/biotechnology.

[113]  Robert C Schuurink,et al.  Regulation of floral scent production in petunia revealed by targeted metabolomics. , 2003, Phytochemistry.

[114]  J Bruce German,et al.  Genomics and metabolomics as markers for the interaction of diet and health: lessons from lipids. , 2003, The Journal of nutrition.

[115]  J. Heijnen,et al.  Metabolic-flux analysis of Saccharomyces cerevisiae CEN.PK113-7D based on mass isotopomer measurements of (13)C-labeled primary metabolites. , 2005, FEMS yeast research.

[116]  P. Schneider,et al.  Long-term kinetic study of beta-carotene, using accelerator mass spectrometry in an adult volunteer. , 2000, Journal of lipid research.

[117]  Martin Hermansson,et al.  Automated quantitative analysis of complex lipidomes by liquid chromatography/mass spectrometry. , 2005, Analytical chemistry.

[118]  D. Schomburg,et al.  GC–MS libraries for the rapid identification of metabolites in complex biological samples , 2005, FEBS letters.

[119]  B. Hammock,et al.  Metabolomics--a new exciting field within the "omics" sciences. , 2004, Environmental health perspectives.

[120]  C. A. Hastings,et al.  New algorithms for processing and peak detection in liquid chromatography/mass spectrometry data. , 2002, Rapid communications in mass spectrometry : RCM.

[121]  U. Roessner,et al.  High-resolution metabolic phenotyping of genetically and environmentally diverse potato tuber systems. Identification of phenocopies. , 2001, Plant physiology.

[122]  Kristian Fog Nielsen,et al.  Fungal metabolite screening: database of 474 mycotoxins and fungal metabolites for dereplication by standardised liquid chromatography-UV-mass spectrometry methodology. , 2003, Journal of chromatography. A.

[123]  G. Mills,et al.  Headspace solid-phase microextraction profiling of volatile compounds in urine: application to metabolic investigations. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

[124]  E Holmes,et al.  Metabonomic characterization of genetic variations in toxicological and metabolic responses using probabilistic neural networks. , 2001, Chemical research in toxicology.

[125]  U. Sauer,et al.  Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS. , 2003, European journal of biochemistry.

[126]  T. Shaler,et al.  Quantification of proteins and metabolites by mass spectrometry without isotopic labeling or spiked standards. , 2003, Analytical chemistry.

[127]  P. Fraser,et al.  Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS. , 2005, Journal of experimental botany.

[128]  J. Frisvad,et al.  Using direct electrospray mass spectrometry in taxonomy and secondary metabolite profiling of crude fungal extracts , 1996 .

[129]  Christian W Klampfl,et al.  Review coupling of capillary electrochromatography to mass spectrometry. , 2004, Journal of chromatography. A.

[130]  Jens Nielsen,et al.  Metabolite profiling of fungi and yeast: from phenotype to metabolome by MS and informatics. , 2005, Journal of experimental botany.

[131]  W. Windig,et al.  A Noise and Background Reduction Method for Component Detection in Liquid Chromatography/Mass Spectrometry , 1996 .

[132]  S. Liu,et al.  Electrospray and tandem mass spectrometry in biochemistry. , 2001, The Biochemical journal.

[133]  M. Hirai,et al.  Integration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[134]  S. Stein,et al.  Deconvolution gas chromatography/mass spectrometry of urinary organic acids--potential for pattern recognition and automated identification of metabolic disorders. , 1999, Rapid communications in mass spectrometry : RCM.

[135]  D. Goodenowe,et al.  Nontargeted metabolome analysis by use of Fourier Transform Ion Cyclotron Mass Spectrometry. , 2002, Omics : a journal of integrative biology.

[136]  J. François,et al.  A rapid and reliable method for metabolite extraction in yeast using boiling buffered ethanol , 1997, Yeast.

[137]  D. Chace,et al.  Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. , 2003, Clinical chemistry.

[138]  P. Schneider,et al.  Quantitation of in vivo human folate metabolism. , 2004, The American journal of clinical nutrition.

[139]  R. Takors,et al.  Quantification of intracellular metabolites in Escherichia coli K12 using liquid chromatographic-electrospray ionization tandem mass spectrometric techniques. , 2001, Analytical biochemistry.

[140]  A. Marshall,et al.  Fourier transform ion cyclotron resonance mass spectrometry: a primer. , 1998, Mass spectrometry reviews.

[141]  Lothar Willmitzer,et al.  Kinetics of labelling of organic and amino acids in potato tubers by gas chromatography-mass spectrometry following incubation in (13)C labelled isotopes. , 2004, The Plant journal : for cell and molecular biology.

[142]  S. Stein.  An integrated method for spectrum extraction and compound identification from gas chromatography/mass spectrometry data , 1999 .

[143]  R. Abagyan,et al.  METLIN: A Metabolite Mass Spectral Database , 2005, Therapeutic drug monitoring.

[144]  Marc K Hellerstein,et al.  New stable isotope-mass spectrometric techniques for measuring fluxes through intact metabolic pathways in mammalian systems: introduction of moving pictures into functional genomics and biochemical phenotyping. , 2004, Metabolic engineering.

[145]  Pierre Marquet,et al.  LC-MS/MS systematic toxicological analysis: comparison of MS/MS spectra obtained with different instruments and settings. , 2005, Clinical biochemistry.

[146]  W. Naidong,et al.  Bioanalytical liquid chromatography tandem mass spectrometry methods on underivatized silica columns with aqueous/organic mobile phases. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.