Ultra high performance liquid chromatography as a tool for the discovery and the analysis of biomarkers of diseases: a review.

The development and use of UHPLC-based methods for the identification, validation and analysis of biomarkers for diseases is reviewed. The currents trends in types of stationary phases and modes of detection are discussed. Afterwards, examples are provided on the use of UHPLC-MS for finding novel biomarkers in samples from in vitro or in vivo animal models of human diseases, as well as in biofluid samples (mainly urine and plasma) obtained from patients. Molecular profiling and targeted analysis are considered, providing an overview of recent experimental or clinical works carried out using UHPLC analysis of compounds from various chemical classes, such as low molecular weight metabolites, hormones, lipids, peptides and proteins.

[1]  S. Song,et al.  Newborn screening for galactosemia by a second-tier multiplex enzyme assay using UPLC-MS/MS in dried blood spots , 2011, Journal of Inherited Metabolic Disease.

[2]  R. Abagyan,et al.  XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. , 2006, Analytical chemistry.

[3]  F. Tingley,et al.  Development and validation of a sample stabilization strategy and a UPLC-MS/MS method for the simultaneous quantitation of acetylcholine (ACh), histamine (HA), and its metabolites in rat cerebrospinal fluid (CSF). , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[4]  E. Endert,et al.  Determination of thyroid hormones and their metabolites in tissue using SPE UPLC-tandem MS. , 2012, Biomedical chromatography : BMC.

[5]  E. Nevedomskaya,et al.  Fibrinogen alpha chain O-glycopeptides as possible markers of urinary tract infection. , 2012, Journal of proteomics.

[6]  Erin E. Chambers,et al.  Quantitation of amyloid beta peptides Aβ(1-38), Aβ(1-40), and Aβ(1-42) in human cerebrospinal fluid by ultra-performance liquid chromatography-tandem mass spectrometry. , 2011, Analytical biochemistry.

[7]  Walter A. Korfmacher,et al.  Ultra-performance liquid chromatography/tandem mass spectrometric determination of testosterone and its metabolites in in vitro samples. , 2006, Rapid communications in mass spectrometry : RCM.

[8]  J. Mazzeo,et al.  Advancing LC Performance with Smaller Particles and Higher Pressure , 2005 .

[9]  T. Toyo’oka,et al.  Practical analytical approach for the identification of biomarker candidates in prediabetic state based upon metabonomic study by ultraperformance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry. , 2010, Journal of proteome research.

[10]  Jean W. Lee,et al.  Method validation of protein biomarkers in support of drug development or clinical diagnosis/prognosis. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[11]  Albert J Fornace,et al.  Radiation Metabolomics. 1. Identification of Minimally Invasive Urine Biomarkers for Gamma-Radiation Exposure in Mice , 2008, Radiation research.

[12]  M. Jensen,et al.  Measuring long-chain acyl-coenzyme A concentrations and enrichment using liquid chromatography/tandem mass spectrometry with selected reaction monitoring. , 2011, Rapid communications in mass spectrometry : RCM.

[13]  T. Toyo’oka,et al.  Rapid, sensitive and simultaneous determination of fluorescence-labeled polyamines in human hair by high-pressure liquid chromatography coupled with electrospray-ionization time-of-flight mass spectrometry. , 2008, Journal of chromatography. A.

[14]  Stephen J. Bruce,et al.  Global metabolic profiling analysis on human urine by UPLC-TOFMS: issues and method validation in nutritional metabolomics. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[15]  Oliver Fiehn,et al.  A comprehensive urinary metabolomic approach for identifying kidney cancerr. , 2007, Analytical biochemistry.

[16]  Hiroki Nakanishi,et al.  Analysis of oxidized phosphatidylcholines as markers for oxidative stress, using multiple reaction monitoring with theoretically expanded data sets with reversed-phase liquid chromatography/tandem mass spectrometry. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[17]  Lanjuan Li,et al.  Metabonomic profiles discriminate hepatocellular carcinoma from liver cirrhosis by ultraperformance liquid chromatography-mass spectrometry. , 2012, Journal of proteome research.

[18]  J. Konje,et al.  The plasma levels of the endocannabinoid, anandamide, increase with the induction of labour , 2010, BJOG : an international journal of obstetrics and gynaecology.

[19]  J. Dufour,et al.  Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling. , 2011, Cancer research.

[20]  Xi-jun Wang,et al.  Ultra-performance liquid chromatography coupled to mass spectrometry as a sensitive and powerful technology for metabolomic studies. , 2011, Journal of separation science.

[21]  M. Zheng,et al.  Urinary metabolic profiling of colorectal carcinoma based on online affinity solid phase extraction-high performance liquid chromatography and ultra performance liquid chromatography-mass spectrometry. , 2010, Molecular bioSystems.

[22]  Chunfu Wu,et al.  Urinary metabonomic study on biochemical changes in chronic unpredictable mild stress model of depression. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[23]  D. Mock,et al.  Measurement of 3-hydroxyisovaleric acid in urine from marginally biotin-deficient humans by UPLC-MS/MS , 2011, Analytical and bioanalytical chemistry.

[24]  N. Sadagopan,et al.  Development of a multiplex UPLC-MRM MS method for quantification of human membrane transport proteins OATP1B1, OATP1B3 and OATP2B1 in in vitro systems and tissues. , 2012, Analytica chimica acta.

[25]  A. Taylor,et al.  Ultra performance liquid chromatography tandem mass spectrometry method for the measurement of anandamide in human plasma. , 2008, Analytical biochemistry.

[26]  A. Garg,et al.  The determination of urinary free and conjugated cortisol using UPLC-MS/MS. , 2011, Bioanalysis.

[27]  Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits , 2010, Metabolomics.

[28]  T. Ebbels,et al.  Optimized preprocessing of ultra-performance liquid chromatography/mass spectrometry urinary metabolic profiles for improved information recovery. , 2011, Analytical chemistry.

[29]  G. Meinlschmidt,et al.  Simultaneous measurement of endogenous cortisol, cortisone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in nails by use of UPLC–MS–MS , 2011, Analytical and bioanalytical chemistry.

[30]  Michael E. Lassman,et al.  A rapid method for cross-species quantitation of apolipoproteins A1, B48 and B100 in plasma by ultra-performance liquid chromatography/tandem mass spectrometry. , 2012, Rapid communications in mass spectrometry : RCM.

[31]  Liang Li,et al.  Ultra-high performance liquid chromatography tandem mass spectrometry for comprehensive analysis of urinary acylcarnitines. , 2011, Analytica chimica acta.

[32]  Chuan-Ho Tang,et al.  Glycerophosphocholine molecular species profiling in the biological tissue using UPLC/MS/MS. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[33]  M. Churchwell,et al.  Improving LC-MS sensitivity through increases in chromatographic performance: comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[34]  T. Marczylo,et al.  Simultaneous measurement of three N-acylethanolamides in human bio-matrices using ultra performance liquid chromatography-tandem mass spectrometry , 2010, Analytical and bioanalytical chemistry.

[35]  S. Palmer,et al.  Rapid determination of C4-acylcarnitine and C5-acylcarnitine isomers in plasma and dried blood spots by UPLC-MS/MS as a second tier test following flow-injection MS/MS acylcarnitine profile analysis. , 2010, Molecular genetics and metabolism.

[36]  U. Steuerwald,et al.  Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography–tandem mass spectrometry , 2011, Steroids.

[37]  Qian Yang,et al.  Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse. , 2010, Journal of proteome research.

[38]  A. Amoako,et al.  Anandamide levels in human female reproductive tissues: solid-phase extraction and measurement by ultraperformance liquid chromatography tandem mass spectrometry. , 2010, Analytical biochemistry.

[39]  Serge Rudaz,et al.  New trends in fast and high-resolution liquid chromatography: a critical comparison of existing approaches , 2010, Analytical and bioanalytical chemistry.

[40]  S. Song,et al.  Multiplex enzyme assay for galactosemia using ultraperformance liquid chromatography-tandem mass spectrometry. , 2010, Clinical chemistry.

[41]  E. Nevedomskaya,et al.  Metabolic profiling of human urine by CE-MS using a positively charged capillary coating and comparison with UPLC-MS. , 2011, Molecular bioSystems.

[42]  M. Lee,et al.  Practical aspects of ultrahigh pressure capillary liquid chromatography. , 2001, Journal of chromatography. A.

[43]  L. Chiandetti,et al.  Simultaneous quantitative determination of N(G),N(G)-dimethyl-L-arginine or asymmetric dimethylarginine and related pathway's metabolites in biological fluids by ultrahigh-performance liquid chromatography/electrospray ionization-tandem mass spectrometry. , 2010, Analytica chimica acta.

[44]  Albert Koulman,et al.  From differentiating metabolites to biomarkers , 2009, Analytical and bioanalytical chemistry.

[45]  T. Toyo’oka,et al.  Hair analysis of histamine and several metabolites in C3H/HeNCrj mice by ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry (UPLC-ESI-TOF-MS): influence of hair cycle and age. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[46]  Asaph Aharoni,et al.  Evaluation of peak picking quality in LC-MS metabolomics data. , 2010, Analytical chemistry.

[47]  G. Luo,et al.  A metabonomic approach applied to predict patients with cerebral infarction. , 2011, Talanta.

[48]  B. Koletzko,et al.  Nonesterified fatty acid determination for functional lipidomics: comprehensive ultrahigh performance liquid chromatography-tandem mass spectrometry quantitation, qualification, and parameter prediction. , 2012, Analytical chemistry.

[49]  Georgios Theodoridis,et al.  UPLC-MS-based analysis of human plasma for metabonomics using solvent precipitation or solid phase extraction. , 2009, Journal of proteome research.

[50]  Tao Zhang,et al.  Discrimination between malignant and benign ovarian tumors by plasma metabolomic profiling using ultra performance liquid chromatography/mass spectrometry. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[51]  T. Ebbels,et al.  Optimization and evaluation of metabolite extraction protocols for untargeted metabolic profiling of liver samples by UPLC-MS. , 2010, Analytical chemistry.

[52]  G. Luo,et al.  Intrarenal metabolomics reveals the association of local organic toxins with the progression of diabetic kidney disease. , 2012, Journal of pharmaceutical and biomedical analysis.

[53]  Alexander Amberg,et al.  Intra- and interlaboratory reproducibility of ultra performance liquid chromatography-time-of-flight mass spectrometry for urinary metabolic profiling. , 2012, Analytical chemistry.

[54]  Ronan M. T. Fleming,et al.  Monitoring metabolites consumption and secretion in cultured cells using ultra-performance liquid chromatography quadrupole–time of flight mass spectrometry (UPLC–Q–ToF-MS) , 2011, Analytical and Bioanalytical Chemistry.

[55]  P. He,et al.  Plasma metabolic profiling of Alzheimer's disease by liquid chromatography/mass spectrometry. , 2010, Clinical biochemistry.

[56]  Laura K. Schnackenberg,et al.  Metabonomics evaluations of age-related changes in the urinary compositions of male Sprague Dawley rats and effects of data normalization methods on statistical and quantitative analysis , 2007, BMC Bioinformatics.

[57]  E. Want,et al.  Seminal oligouridinosis: low uridine secretion as a biomarker for infertility in spinal neurotrauma. , 2008, Clinical chemistry.

[58]  Lanjuan Li,et al.  Fecal metabolome profiling of liver cirrhosis and hepatocellular carcinoma patients by ultra performance liquid chromatography-mass spectrometry. , 2011, Analytica chimica acta.

[59]  K. Blennow,et al.  Biomarker-based dissection of neurodegenerative diseases , 2011, Progress in Neurobiology.

[60]  A. Zhang,et al.  Metabolomic study of insomnia and intervention effects of Suanzaoren decoction using ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry. , 2012, Journal of pharmaceutical and biomedical analysis.

[61]  Peiyuan Yin,et al.  Metabonomics study of intestinal fistulas based on ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC/Q-TOF MS). , 2006, Journal of proteome research.

[62]  Haitao Lv,et al.  Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples. , 2008, Journal of separation science.

[63]  J. Bierau,et al.  Quantitative UPLC-MS/MS analysis of underivatised amino acids in body fluids is a reliable tool for the diagnosis and follow-up of patients with inborn errors of metabolism. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[64]  R. Obeid,et al.  Simultaneous quantification of S-adenosyl methionine and S-adenosyl homocysteine in human plasma by stable-isotope dilution ultra performance liquid chromatography tandem mass spectrometry. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[65]  P. Sherwood,et al.  Rapid, simultaneous quantitation of mono and dioxygenated metabolites of arachidonic acid in human CSF and rat brain. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[66]  J. H. Lee,et al.  Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). , 2010, Journal of proteome research.

[67]  P. Solich,et al.  Comparison of a novel ultra-performance liquid chromatographic method for determination of retinol and α-tocopherol in human serum with conventional HPLC using monolithic and particulate columns , 2007, Analytical and bioanalytical chemistry.

[68]  J. Jorgenson,et al.  Ultrahigh-pressure reversed-phase liquid chromatography in packed capillary columns. , 1997, Analytical chemistry.

[69]  B. Pachkowski,et al.  Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine by ultra high pressure liquid chromatography-heat assisted electrospray ionization-tandem mass spectrometry. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[70]  T. Toyo’oka,et al.  Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of diabetic mice based upon metabolite profiling using ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry. , 2011, Clinica chimica acta; international journal of clinical chemistry.

[71]  C. Creaser,et al.  Determination of testosterone and epitestosterone glucuronides in urine by ultra performance liquid chromatography-ion mobility-mass spectrometry. , 2011, The Analyst.

[72]  O. Al-Dirbashi,et al.  Analysis of organic acid markers relevant to inherited metabolic diseases by ultra-performance liquid chromatography/tandem mass spectrometry as benzofurazan derivatives. , 2007, Rapid communications in mass spectrometry : RCM.

[73]  Steffen Neumann,et al.  Critical assessment of alignment procedures for LC-MS proteomics and metabolomics measurements , 2008, BMC Bioinformatics.

[74]  T. Toyo’oka,et al.  Rapid determination of histamine and its metabolites in mice hair by ultra-performance liquid chromatography with time-of-flight mass spectrometry. , 2006, Journal of chromatography. A.

[75]  Xi-jun Wang,et al.  Exploratory urinary metabolic biomarkers and pathways using UPLC-Q-TOF-HDMS coupled with pattern recognition approach. , 2012, The Analyst.

[76]  Tianlu Chen,et al.  Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. , 2009, Journal of proteome research.

[77]  T. Henriksen,et al.  Automated method for the direct analysis of 8-oxo-guanosine and 8-oxo-2'-deoxyguanosine in human urine using ultraperformance liquid chromatography and tandem mass spectrometry. , 2009, Free radical biology & medicine.

[78]  I. Wilson,et al.  Evaluation of the repeatability of ultra-performance liquid chromatography-TOF-MS for global metabolic profiling of human urine samples. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[79]  John N Weinstein,et al.  UPLC-ESI-TOFMS-based metabolomics and gene expression dynamics inspector self-organizing metabolomic maps as tools for understanding the cellular response to ionizing radiation. , 2008, Analytical chemistry.

[80]  Weidong Zhang,et al.  Metabolomic study of myocardial ischemia and intervention effects of Compound Danshen Tablets in rats using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. , 2010, Journal of pharmaceutical and biomedical analysis.

[81]  D. Prvulovic,et al.  Biomarkers for major depression and its delineation from neurodegenerative disorders , 2011, Progress in Neurobiology.

[82]  S. Ng,et al.  Sub-2 μm porous silica materials for enhanced separation performance in liquid chromatography. , 2012, Journal of chromatography. A.

[83]  L. Denoroy,et al.  A rapid and sensitive method for the analysis of brain monoamine neurotransmitters using ultra-fast liquid chromatography coupled to electrochemical detection. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[84]  Frank Dieterle,et al.  New technologies around biomarkers and their interplay with drug development , 2008, Analytical and bioanalytical chemistry.

[85]  Caroline H. Johnson,et al.  Radiation Metabolomics. 4. UPLC-ESI-QTOFMS-Based Metabolomics for Urinary Biomarker Discovery in Gamma-Irradiated Rats , 2011, Radiation research.

[86]  M. Orešič,et al.  Data processing for mass spectrometry-based metabolomics. , 2007, Journal of chromatography. A.

[87]  T. Toyo’oka,et al.  Determination of DL-amino acids, derivatized with R(-)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole, in nail of diabetic patients by UPLC-ESI-TOF-MS. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[88]  Yanqun Sun,et al.  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. , 2011, Journal of pharmaceutical and biomedical analysis.

[89]  I. Wilson,et al.  Metabolite profiles from dried biofluid spots for metabonomic studies using UPLC combined with oaToF-MS. , 2010, Journal of proteome research.

[90]  J. Ingle,et al.  Evaluation of serum estrogen-DNA adducts as potential biomarkers for breast cancer risk , 2012, The Journal of Steroid Biochemistry and Molecular Biology.

[91]  E. Schaftingen,et al.  A lymphoblast model for IDH2 gain-of-function activity in d-2-hydroxyglutaric aciduria type II: novel avenues for biochemical and therapeutic studies. , 2011, Biochimica et biophysica acta.

[92]  I. Wilson,et al.  Does the mass spectrometer define the marker? A comparison of global metabolite profiling data generated simultaneously via UPLC-MS on two different mass spectrometers. , 2010, Analytical chemistry.

[93]  N. Kitteringham,et al.  Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[94]  I. Wilson,et al.  Metabolite profiles from dried blood spots for metabonomic studies using UPLC combined with orthogonal acceleration ToF-MS: effects of different papers and sample storage stability. , 2011, Bioanalysis.

[95]  Guowang Xu,et al.  Metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry. , 2012, Molecular bioSystems.

[96]  Stephen J. Bruce,et al.  Investigation of human blood plasma sample preparation for performing metabolomics using ultrahigh performance liquid chromatography/mass spectrometry. , 2009, Analytical chemistry.

[97]  Oliver Fiehn,et al.  Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research , 2009, Metabolomics.

[98]  Guowang Xu,et al.  Urinary profiling investigation of metabolites with cis-diol structure from cancer patients based on UPLC-MS and HPLC-MS as well as multivariate statistical analysis. , 2006, Journal of separation science.

[99]  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.

[100]  P. Hu,et al.  Metabolomic profiling of rat serum associated with isoproterenol-induced myocardial infarction using ultra-performance liquid chromatography/time-of-flight mass spectrometry and multivariate analysis. , 2009, Talanta.

[101]  A. Cheema,et al.  Metabolomics of Human Intestinal Transplant Rejection , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[102]  Z. Cai,et al.  Metabolomics study of alcohol-induced liver injury and hepatocellular carcinoma xenografts in mice. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[103]  P. Swart,et al.  The development of an ultra performance liquid chromatography-coupled atmospheric pressure chemical ionization mass spectrometry assay for seven adrenal steroids. , 2008, Analytical biochemistry.

[104]  J. Nicholson,et al.  Novel application of reversed-phase UPLC-oaTOF-MS for lipid analysis in complex biological mixtures: a new tool for lipidomics. , 2007, Journal of proteome research.

[105]  Richard G Kay,et al.  The application of ultra-performance liquid chromatography/tandem mass spectrometry to the detection and quantitation of apolipoproteins in human serum. , 2007, Rapid communications in mass spectrometry : RCM.

[106]  R. Zhu,et al.  Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone. , 2012, Journal of proteome research.

[107]  J. Donnelly,et al.  Plasma citrulline measurement using UPLC tandem mass-spectrometry to determine small intestinal enterocyte pathology. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[108]  A. Fornace,et al.  UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model. , 2011, Journal of proteome research.

[109]  B. Jung,et al.  Investigation of endogenous metabolic changes in the urine of pseudo germ-free rats using a metabolomic approach. , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[110]  Xiaoying Zheng,et al.  Metabonomic study on women of reproductive age treated with nutritional intervention: screening potential biomarkers related to neural tube defects occurrence. , 2011, Biomedical chromatography : BMC.

[111]  Albert J. Fornace,et al.  Metabolomic Analysis in Severe Childhood Pneumonia in The Gambia, West Africa: Findings from a Pilot Study , 2010, PloS one.

[112]  I. Wilson,et al.  The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry. , 2006, Rapid communications in mass spectrometry : RCM.

[113]  Ji Jiang,et al.  Measurement of 1- and 3-methylhistidine in human urine by ultra performance liquid chromatography-tandem mass spectrometry. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[114]  D. Kell,et al.  Metabolic profiling of serum using Ultra Performance Liquid Chromatography and the LTQ-Orbitrap mass spectrometry system. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[115]  Xin Lu,et al.  Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry. , 2010, Molecular bioSystems.

[116]  G. Siuzdak,et al.  Nonlinear data alignment for UPLC-MS and HPLC-MS based metabolomics: quantitative analysis of endogenous and exogenous metabolites in human serum. , 2006, Analytical chemistry.

[117]  John M. Pisciotta,et al.  Sensitive and rapid method for amino acid quantitation in malaria biological samples using AccQ.Tag ultra performance liquid chromatography-electrospray ionization-MS/MS with multiple reaction monitoring. , 2010, Analytical chemistry.

[118]  Jennifer H Granger,et al.  A rapid screening approach to metabonomics using UPLC and oa-TOF mass spectrometry: application to age, gender and diurnal variation in normal/Zucker obese rats and black, white and nude mice. , 2005, The Analyst.

[119]  N. Heaton,et al.  Bile UPLC‐MS fingerprinting and bile acid fluxes during human liver transplantation , 2011, Electrophoresis.

[120]  Pauline M Rudd,et al.  Ultra performance liquid chromatographic profiling of serum N-glycans for fast and efficient identification of cancer associated alterations in glycosylation. , 2010, Analytical chemistry.

[121]  I. Wilson,et al.  A metabonomic study of strain- and age-related differences in the Zucker rat. , 2007, Rapid communications in mass spectrometry : RCM.

[122]  M. Morris,et al.  Serum steroid profiling for congenital adrenal hyperplasia using liquid chromatography-tandem mass spectrometry. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[123]  J. Ordovás,et al.  Liquid chromatography-mass spectrometry methods for urinary biomarker detection in metabonomic studies with application to nutritional studies. , 2009, Biomedical chromatography : BMC.

[124]  Minli Zhang,et al.  Rapid quantitation of testosterone hydroxyl metabolites by ultra-performance liquid chromatography and mass spectrometry. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[125]  Zhi-Yong Wang,et al.  Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease , 2011, Brain Research.

[126]  C. Guillou,et al.  Critical aspects of urine profiling for the selection of potential biomarkers using UPLC-TOF-MS. , 2012, Biomedical chromatography : BMC.

[127]  Y. Li,et al.  Metabolic profiling of urine in young obese men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC/Q-TOF MS). , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[128]  J. Fekete,et al.  Fast liquid chromatography: the domination of core-shell and very fine particles. , 2012, Journal of chromatography. A.

[129]  G. Karthikeyan,et al.  Progressive degradation of serum samples limits proteomic biomarker discovery. , 2009, Analytical biochemistry.

[130]  Johan Trygg,et al.  Evaluation of a protocol for metabolic profiling studies on human blood plasma by combined ultra-performance liquid chromatography/mass spectrometry: From extraction to data analysis. , 2008, Analytical biochemistry.

[131]  G. Frost,et al.  An approach towards method development for untargeted urinary metabolite profiling in metabonomic research using UPLC/QToF MS. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[132]  Serge Rudaz,et al.  Knowledge discovery in metabolomics: an overview of MS data handling. , 2010, Journal of separation science.

[133]  Chengjie Ji,et al.  Simultaneous determination of plasma epinephrine and norepinephrine using an integrated strategy of a fully automated protein precipitation technique, reductive ethylation labeling and UPLC-MS/MS. , 2010, Analytica chimica acta.

[134]  Liang Li,et al.  A method for comprehensive analysis of urinary acylglycines by using ultra-performance liquid chromatography quadrupole linear ion trap mass spectrometry , 2010, Journal of the American Society for Mass Spectrometry.

[135]  L. Drahos,et al.  Investigation of genetic variants of α-1 acid glycoprotein by ultra-performance liquid chromatography–mass spectrometry , 2009, Analytical and bioanalytical chemistry.

[136]  T. D. de Koning,et al.  Quantification of vitamin B6 vitamers in human cerebrospinal fluid by ultra performance liquid chromatography-tandem mass spectrometry. , 2012, Analytica chimica acta.

[137]  Xin Lu,et al.  Method for liver tissue metabolic profiling study and its application in type 2 diabetic rats based on ultra performance liquid chromatography-mass spectrometry. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[138]  R. Ophoff,et al.  A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of D-amino acids in body fluids. , 2011, Journal of chromatography. A.

[139]  A. Matsubara,et al.  A metabonomic approach identifies human urinary phenylacetylglutamine as a novel marker of interstitial cystitis. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[140]  I. Wilson,et al.  High temperature-ultra performance liquid chromatography-mass spectrometry for the metabonomic analysis of Zucker rat urine. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[141]  Shelly C. Lu,et al.  Liquid chromatography-mass spectrometry-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of nonalcoholic fatty liver disease. , 2010, Journal of proteome research.

[142]  I. Wilson,et al.  Liquid chromatography and ultra-performance liquid chromatography-mass spectrometry fingerprinting of human urine: sample stability under different handling and storage conditions for metabonomics studies. , 2008, Journal of chromatography. A.

[143]  Hui Sun,et al.  Pattern recognition approaches and computational systems tools for ultra performance liquid chromatography-mass spectrometry-based comprehensive metabolomic profiling and pathways analysis of biological data sets. , 2012, Analytical chemistry.

[144]  Joshua D. Knowles,et al.  Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry , 2011, Nature Protocols.

[145]  J. Chen,et al.  Metabonomics study of atherosclerosis rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry. , 2009, Talanta.

[146]  Z. Ryoo,et al.  Proteomic analysis of protein expression affected by peroxiredoxin V knock-down in hypoxic kidney. , 2010, Journal of proteome research.

[147]  A. Amoako,et al.  Quantitative analysis of anandamide and related acylethanolamides in human seminal plasma by ultra performance liquid chromatography tandem mass spectrometry. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[148]  Ian D Wilson,et al.  Hydrophilic interaction and reversed-phase ultra-performance liquid chromatography TOF-MS for metabonomic analysis of Zucker rat urine. , 2008, Journal of separation science.

[149]  Jerzy Silberring,et al.  Biomarker discovery and clinical proteomics. , 2010, Trends in analytical chemistry : TRAC.

[150]  E. Hill,et al.  Methodology for profiling the steroid metabolome in animal tissues using ultraperformance liquid chromatography-electrospray-time-of-flight mass spectrometry. , 2008, Analytical chemistry.

[151]  R. Obeid,et al.  Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[152]  Rainer Breitling,et al.  Separating the wheat from the chaff: a prioritisation pipeline for the analysis of metabolomics datasets , 2011, Metabolomics.

[153]  Y. Shiloh,et al.  Simultaneous identification and quantification of proteins by differential (16)O/(18)O labeling and UPLC-MS/MS applied to mouse cerebellar phosphoproteome following irradiation. , 2009, Anticancer research.

[154]  Ming-zhu Yin,et al.  Identification of metabolic biomarkers to diagnose epithelial ovarian cancer using a UPLC/QTOF/MS platform , 2012, Acta oncologica.

[155]  Joshua D. Knowles,et al.  Development of a robust and repeatable UPLC-MS method for the long-term metabolomic study of human serum. , 2009, Analytical chemistry.

[156]  M. Evans,et al.  Rapid measurement of 8-oxo-7,8-dihydro-2′-deoxyguanosine in human biological matrices using ultra-high-performance liquid chromatography–tandem mass spectrometry , 2012, Free radical biology & medicine.

[157]  Xiaomei Yan,et al.  Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system. , 2009, Analytica chimica acta.

[158]  R. Obeid,et al.  Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[159]  N. Longo,et al.  Use of Steroid Profiling by UPLC-MS/MS as a Second Tier Test in Newborn Screening for Congenital Adrenal Hyperplasia: The Utah Experience , 2009, Pediatric Research.

[160]  I. García-Pérez,et al.  Chemometric analysis of urine fingerprints acquired by liquid chromatography‐mass spectrometry and capillary electrophoresis: Application to the schistosomiasis mouse model , 2010, Electrophoresis.

[161]  P. Rudd,et al.  High throughput plasma N-glycome profiling using multiplexed labelling and UPLC with fluorescence detection. , 2011, The Analyst.

[162]  Z. Cai,et al.  Metabolite profiling of plasma and urine from rats with TNBS‐induced acute colitis using UPLC‐ESI‐QTOF‐MS‐based metabonomics – a pilot study , 2012, The FEBS journal.

[163]  B. Avery,et al.  Urinary excretion study of coenzyme Q10 in rats by ultra-performance liquid chromatography-mass spectrometry. , 2008, Journal of chromatographic science.

[164]  Kirill Veselkov,et al.  UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers. , 2012, Molecular bioSystems.

[165]  James F Rusling,et al.  Measurement of biomarker proteins for point-of-care early detection and monitoring of cancer. , 2010, The Analyst.

[166]  Yiyu Cheng,et al.  Ultra-High Performance Liquid Chromatography–Mass Spectrometry for the Metabolomic Analysis of Urine in Colorectal Cancer , 2008, Digestive Diseases and Sciences.

[167]  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.

[168]  Mahlet G Tadesse,et al.  Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis. , 2012, Analytica chimica acta.

[169]  I. Wilson,et al.  Application of ultra performance liquid chromatography-mass spectrometry to profiling rat and dog bile. , 2009, Journal of proteome research.

[170]  R. Kozak,et al.  Diethylation labeling combined with UPLC/MS/MS for simultaneous determination of a panel of monoamine neurotransmitters in rat prefrontal cortex microdialysates. , 2008, Analytical chemistry.

[171]  E. Want,et al.  Liquid chromatography-mass spectrometry based global metabolite profiling: a review. , 2012, Analytica chimica acta.

[172]  T. Toyo’oka,et al.  Metabolic profiling of rat hair and screening biomarkers using ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry. , 2007, Journal of chromatography. A.

[173]  I. Wilson,et al.  Profiling biological samples using ultra performance liquid chromatography-inductively coupled plasma-mass spectrometry (UPLC-ICP-MS) for the determination of phosphorus and sulfur-containing metabolites. , 2011, Molecular bioSystems.

[174]  L. Dragsted,et al.  Metabolic fingerprinting of high-fat plasma samples processed by centrifugation- and filtration-based protein precipitation delineates significant differences in metabolite information coverage. , 2012, Analytica chimica acta.

[175]  Nick C. Fox,et al.  Biomarkers for Alzheimer's disease therapeutic trials , 2011, Progress in Neurobiology.

[176]  Á. Gil-Izquierdo,et al.  A ultra-pressure liquid chromatography/triple quadrupole tandem mass spectrometry method for the analysis of 13 eicosanoids in human urine and quantitative 24 hour values in healthy volunteers in a controlled constant diet. , 2012, Rapid communications in mass spectrometry : RCM.

[177]  R. Gajbhiye,et al.  Sperm phosphoproteome profiling by ultra performance liquid chromatography followed by data independent analysis (LC-MS(E)) reveals altered proteomic signatures in asthenozoospermia. , 2012, Journal of proteomics.

[178]  Patrick J. Brennan,et al.  Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis , 2011, PLoS neglected tropical diseases.

[179]  Guolan Gao,et al.  Proteomic analysis of human epithelial ovarian cancer xenografts in immunodeficient mice exposed to chronic psychological stress , 2011, Science China Life Sciences.

[180]  I. Wilson,et al.  UPLC/MS(E); a new approach for generating molecular fragment information for biomarker structure elucidation. , 2006, Rapid communications in mass spectrometry : RCM.

[181]  E. Chan,et al.  Ultra-pressure liquid chromatography/tandem mass spectrometry targeted profiling of arachidonic acid and eicosanoids in human colorectal cancer. , 2011, Rapid communications in mass spectrometry : RCM.

[182]  Ying-yong Zhao,et al.  Urinary metabonomics study on biochemical changes in an experimental model of chronic renal failure by adenine based on UPLC Q-TOF/MS. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[183]  K. Lackner,et al.  Quantification of the Fabry marker lysoGb3 in human plasma by tandem mass spectrometry. , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[184]  Y. Xiong,et al.  Blood serum profiling of the rat spinal nerve ligation model using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. , 2009, European journal of pharmacology.

[185]  D. Kell,et al.  Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy. , 2011, Journal of proteome research.

[186]  Xi-jun Wang,et al.  Modern analytical techniques in metabolomics analysis. , 2012, The Analyst.

[187]  C. Creaser,et al.  Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography-ion mobility-mass spectrometry. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[188]  R. Obeid,et al.  Quantification of plasma phospholipids by ultra performance liquid chromatography tandem mass spectrometry , 2011, Analytical and bioanalytical chemistry.

[189]  Y. Mechref,et al.  Biochemical individuality reflected in chromatographic, electrophoretic and mass-spectrometric profiles. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[190]  H. Bøtker,et al.  A UPLC-MS/MS application for profiling of intermediary energy metabolites in microdialysis samples--a method for high-throughput. , 2010, Journal of pharmaceutical and biomedical analysis.

[191]  Tianlu Chen,et al.  Salivary metabolite signatures of oral cancer and leukoplakia , 2011, International journal of cancer.

[192]  A. Fornace,et al.  Radiation Metabolomics. 2. Dose- and Time-Dependent Urinary Excretion of Deaminated Purines and Pyrimidines after Sublethal Gamma-Radiation Exposure in Mice , 2009, Radiation research.