HPLC-MS-based methods for the study of metabonomics.

The development and use of HPLC-MS for the study of metabonomics is reviewed. To date the technique has been applied to the analysis of urine samples obtained from studies in rodents in investigations of physiological variation (e.g., factors such as strain, gender, diurnal variation, etc.) and toxicity. Examples are provided of the use of conventional HPLC, capillary methods and the recently introduced high-resolution systems based on a combination of high pressure and small particle size ("UPLC"). Comparison is also made of the use of 1H NMR spectroscopy and HPLC-MS for the analysis of biofluid samples and the advantages and limitations of the two approaches are assessed. Likely future developments are considered.

[1]  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.

[2]  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.

[3]  J. Lindon,et al.  'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. , 1999, Xenobiotica; the fate of foreign compounds in biological systems.

[4]  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.

[5]  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.

[6]  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.

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

[8]  J. Lindon,et al.  The identification of novel biomarkers of renal toxicity using automatic data reduction techniques and PCA of proton NMR spectra of urine , 1998 .

[9]  I. Wilson,et al.  An NMR‐based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse , 2000, FEBS letters.

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

[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]  Masaru Tomita,et al.  Simultaneous determination of anionic intermediates for Bacillus subtilis metabolic pathways by capillary electrophoresis electrospray ionization mass spectrometry. , 2002, Analytical chemistry.

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

[14]  Anthony F. P. Nash,et al.  A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects. , 2003, Journal of pharmaceutical and biomedical analysis.

[15]  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.

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

[17]  O. Fiehn,et al.  Metabolite profiling for plant functional genomics , 2000, Nature Biotechnology.

[18]  I. Wilson,et al.  Physiological variation in metabolic phenotyping and functional genomic studies: use of orthogonal signal correction and PLS‐DA , 2002, FEBS letters.

[19]  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.