基于液质联用技术的代谢组学生物样本——血液及尿液的收集和处理
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摘要
代谢组学是定性及定量描述内源性代谢物变化的科学,正广泛应用于疾病诊断和预后过程中。血液和尿液是代谢组学研究中常用的生物样本,但因其代谢物繁多、成分复杂,亟须使用灵敏度高、特异性强的分离分析技术。液相色谱-质谱联用(liquid chromatography-mass spectrometry,LC-MS)技术分析速度快、分离效率高,非常适用于代谢组学等方面的研究。生物样本的采集、处理过程是实验中最关键的一步,直接决定着实验结果的准确性,因此生物样本预处理过程的标准化显得尤为重要。本文综述了常用的生物流体—血液和尿液的收集、处理及储存方法,以期为有关代谢组学研究提供参考。
Metabolomics is a science which can describe the alteration levels of endogenous metabolites qualitatively and quantitatively.It has been widely used for disease diagnosis and prognosis.Blood and urine are the most common biological fluids in the study of metabolomics.Since a large number of metabolites and complex components are exerted in blood and urine,it is urgent to use analytic technology with high sensitivity and specificity.With the advantages of fast analysis and high separation efficiency,liquid chromatography-mass spectrometry(LC-MS)technology is especially suitable for metabolomics.It is well known that the collection and preparation of biological samples are the most crucial steps in experiments,which can directly determine the accuracy of the results.Therefore,it is essential to standardize the pretreatment process of biological samples.This article reviewed the procedures of blood and urine collection,preparation and storage using LC-MS technology in the study of metabolomics,which can provide references for related researches.
Metabolomics is a science which can describe the alteration levels of endogenous metabolites qualitatively and quantitatively.It has been widely used for disease diagnosis and prognosis.Blood and urine are the most common biological fluids in the study of metabolomics.Since a large number of metabolites and complex components are exerted in blood and urine,it is urgent to use analytic technology with high sensitivity and specificity.With the advantages of fast analysis and high separation efficiency,liquid chromatography-mass spectrometry(LC-MS)technology is especially suitable for metabolomics.It is well known that the collection and preparation of biological samples are the most crucial steps in experiments,which can directly determine the accuracy of the results.Therefore,it is essential to standardize the pretreatment process of biological samples.This article reviewed the procedures of blood and urine collection,preparation and storage using LC-MS technology in the study of metabolomics,which can provide references for related researches.
引文
[1]Emwas A-H,Luchinat C,Turano P,et al.Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies:a review[J].Metabolomics,2014,11(4):872-894.
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[3]Pinto J,Domingues MR,Galhano E,et al.Human plasma stability during handling and storage:impact on NMR metabolomics[J].Analyst,2014,139(5):1168-1177.
[4]Rist MJ,Muhle-Goll C,Gorling B,et al.Influence of freezing and storage procedure on human urine samples in NMR-based metabolomics[J].Metabolites,2013,3(2):243-258.
[5]Liu L,Aa J,Wang G,et al.Differences in metabolite profile between blood plasma and serum[J].Anal Biochem,2010,406(2):105-112.
[6]Zhang JJ,Jia JP,Qin XM.Applications progress of mass spectrometry in analysis of traditional Chinese medicine[J].JInstrument Anal(分析测试学报),2017,36(5):579-587.
[7]Lopez-Bascon MA,Priego-Capote F,Peralbo-Molina A,et al.Influence of the collection tube on metabolomic changes in serum and plasma[J].Talanta,2016,150:681-689.
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[9]Brauer R,Leichtle AB,Fiedler GM,et al.Preanalytical standardization of amino acid and acylcarnitine metabolite profiling in human blood using tandem mass spectrometry[J].Metabolomics,2010,7(3):344-352.
[10]Townsend MK,Bao Y,Poole EM,et al.Impact of pre-analytic blood sample collection factors on metabolomics[J].Cancer Epidemiol Biomarkers Prev,2016,25(5):823-829.
[11]Winnike JH,Busby MG,Watkins PB,et al.Effects of a prolonged standardized diet on normalizing the human metabolome[J].Am J Clin Nutr,2009,90(6):1496-1501.
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[13]Lin Z.Standardization of collection and pretreatment for metabolomics samples and metabolic sundrome study based on chromatography-mass spectrometry[D].Central South University(中南大学),2014.
[14]Hernandes VV,Barbas C,Dudzik D.A review of blood sample handling and pre-processing for metabolomics studies[J].Electrophoresis,2017,38(18):2232-2241.
[15]Salvagno GL,Danese E,Lippi G.Preanalytical variables for liquid chromatography-mass spectrometry(LC-MS)analysis of human blood specimens[J].Clin Biochem,2017,50(10-11):582-586.
[16]Kamlage B,Maldonado SG,Bethan B,et al.Quality markers addressing preanalytical variations of blood and plasma processing identified by broad and targeted metabolite profiling[J].Clin Chem,2014,60(2):399-412.
[17]Feng L,Cao FR,Liu XM,et al.Sample collection and preparation of untargeted metabolomics[J].Central South Pharmacy(中南药学),2014,2014(12):1217-1221.
[18]Zhang Y,Song YY,Song WY,et al.Factors influencing matrix effects of sabarubicin and its major metabolite in human plasma during liquid chromatography-tandem mass spectrometry analysis[J].Chin J New Drug(中国新药杂志),2016,25(11):1241-1247.
[19]Barri T,Dragsted LO.UPLC-ESI-QTOF/MS and multivariate data analysis for blood plasma and serum metabolomics:effect of experimental artefacts and anticoagulant[J].Anal Chim Acta,2013,768:118-128.
[20]Rao Z,Qin HY,Shao YY,et al.Determination of serotonin concentration in rat plasma by LC-MS/MS with pre-column derivatization[J].J Chin Hosp Pharm(中国医院药学杂志),2015,35(20):1811-1815.
[21]Timms JF,Arslan-Low E,Gentry-Maharaj A,et al.Preanalytic influence of sample handling on SELDI-TOF serum protein profiles[J].Clin Chem,2007,53(4):645-656.
[22]Hirayama A,Sugimoto M,Suzuki A,et al.Effects of processing and storage conditions on charged metabolomic profiles in blood[J].Electrophoresis,2015,36(18):2148-2155.
[23]Jrgenrud B,Jntti S,Mattila I,et al.The influence of sample collection methodology and sample preprocessing on the blood metabolic profle[J].Bioanalysis,2015,7(8):991-1006.
[24]Yu ZH,Kastenmüller G,He Y,et al.Differences between human plasma and serum metabolite profiles[J].Plos One,2011,6(7):e21230.
[25]Yin P,Peter A,Franken H,et al.Preanalytical aspects and sample quality assessment in metabolomics studies of human blood[J].Clin Chem,2013,59(5):833-845.
[26]Trezzi JP,Jger C,Galozzi S,et al.Metabolic profiling of body fluids and multivariate data analysis[J].MethodsX,2017,4:95-103.
[27]Zivkovic AM,Wiest MM,Nguyen UT,et al.Effects of sample handling and storage on quantitative lipid analysis in human serum[J].Metabolomics,2009,5(4):507-516.
[28]Mischak H,Apweiler R,Banks RE,et al.Clinical proteomics:A need to define the field and to begin to set adequate standards[J].Proteomics Clin Appl,2007,1(2):148-156.
[29]Want EJ,Wilson ID,Gika H,et al.Global metabolic profiling procedures for urine using UPLC-MS[J].Nature Protocols,2010,5(6):1005-1018.
[30]Siddiqui NY,DuBois LG,John-Williams LS,et al.Optimizing urine processing protocols for protein and metabolite detection[J].J Proteomics Bioinform,2015,2015(Suppl 14):1-17.
[31]Bernini P,Bertini I,Luchinat C,et al.Standard operating procedures for pre-analytical handling of blood and urine for metabolomic studies and biobanks[J].J Biomol NMR,2011,49(3-4):231-243.
[32]Yuille M,Illig T,Hveem K,et al.Laboratory management of samples in biobanks:European consensus expert group report[J].Biopreserv Biobank,2010,8(1):65-69.
[33]Gika HG,Zisi C,Theodoridis G,et al.Protocol for quality control in metabolic profiling of biological fluids by U(H)PLC-MS[J].J Chromatogr B Analyt Technol Biomed Life Sci,2016,1008:15-25.
[34]Wang Y,Caldwell R,Cowan DA,et al.LC-MS-based metabolomics discovers purine endogenous associations with low-dose salbutamol in urine collected for antidoping tests[J].Anal Chem,2016,88(4):2243-2249.
[35]Khamis MM,Adamko DJ,El-Aneed A.Mass spectrometric based approaches in urine metabolomics and biomarker discovery[J].Mass Spectrom Rev,2017,36(2):115-134.
[36]Emwas AH,Al-Talla ZA,Kharbatia NM.Sample collection and preparation of biofluids and extracts for gas chromatography-mass spectrometry[J].Methods Mol Biol,2015,1277:75-90.
[37]Emwas AH,Roy R,McKay RT,et al.Recommendations and standardization of biomarker quantification using NMR-based metabolomics with particular focus on urinary analysis[J].JProteome Res,2016,15(2):360-373.
[38]Saude EJ,Sykes BD.Urine stability for metabolomic studies:effects of preparation and storage[J].Metabolomics,2007,3(1):19-27.
[39]Gika HG,Theodoridis GA,Wilson ID.Liquid chromatography and ultra-performance liquid chromatography-mass spectrometry fingerprinting of human urine:sample stability under different handling and storage conditions for metabonomics studies[J].J Chromatogr A,2008,1189(1-2):314-322.
[40]Vuckovic D.Current trends and challenges in sample preparation for global metabolomics using liquid chromatographymass spectrometry[J].Anal Bioanal Chem,2012,403(6):1523-1548.
[2]Trivedi DK,Jones H,Shah A,et al.Development of zwitterionic hydrophilic liquid chromatography(ZIC HILIC-MS)metabolomics method for shotgun analysis of human urine[J].J Chromat Separation Techniq,2012,3(6):144-155.
[3]Pinto J,Domingues MR,Galhano E,et al.Human plasma stability during handling and storage:impact on NMR metabolomics[J].Analyst,2014,139(5):1168-1177.
[4]Rist MJ,Muhle-Goll C,Gorling B,et al.Influence of freezing and storage procedure on human urine samples in NMR-based metabolomics[J].Metabolites,2013,3(2):243-258.
[5]Liu L,Aa J,Wang G,et al.Differences in metabolite profile between blood plasma and serum[J].Anal Biochem,2010,406(2):105-112.
[6]Zhang JJ,Jia JP,Qin XM.Applications progress of mass spectrometry in analysis of traditional Chinese medicine[J].JInstrument Anal(分析测试学报),2017,36(5):579-587.
[7]Lopez-Bascon MA,Priego-Capote F,Peralbo-Molina A,et al.Influence of the collection tube on metabolomic changes in serum and plasma[J].Talanta,2016,150:681-689.
[8]Yin P,Lehmann R,Xu G.Effects of pre-analytical processes on blood samples used in metabolomics studies[J].Anal Bioanal Chem,2015,407(17):4879-4892.
[9]Brauer R,Leichtle AB,Fiedler GM,et al.Preanalytical standardization of amino acid and acylcarnitine metabolite profiling in human blood using tandem mass spectrometry[J].Metabolomics,2010,7(3):344-352.
[10]Townsend MK,Bao Y,Poole EM,et al.Impact of pre-analytic blood sample collection factors on metabolomics[J].Cancer Epidemiol Biomarkers Prev,2016,25(5):823-829.
[11]Winnike JH,Busby MG,Watkins PB,et al.Effects of a prolonged standardized diet on normalizing the human metabolome[J].Am J Clin Nutr,2009,90(6):1496-1501.
[12]Bowen RA,Remaley AT.Interferences from blood collection tube components on clinical chemistry assays[J].Biochem Med(Zagreb),2014,24(1):31-44.
[13]Lin Z.Standardization of collection and pretreatment for metabolomics samples and metabolic sundrome study based on chromatography-mass spectrometry[D].Central South University(中南大学),2014.
[14]Hernandes VV,Barbas C,Dudzik D.A review of blood sample handling and pre-processing for metabolomics studies[J].Electrophoresis,2017,38(18):2232-2241.
[15]Salvagno GL,Danese E,Lippi G.Preanalytical variables for liquid chromatography-mass spectrometry(LC-MS)analysis of human blood specimens[J].Clin Biochem,2017,50(10-11):582-586.
[16]Kamlage B,Maldonado SG,Bethan B,et al.Quality markers addressing preanalytical variations of blood and plasma processing identified by broad and targeted metabolite profiling[J].Clin Chem,2014,60(2):399-412.
[17]Feng L,Cao FR,Liu XM,et al.Sample collection and preparation of untargeted metabolomics[J].Central South Pharmacy(中南药学),2014,2014(12):1217-1221.
[18]Zhang Y,Song YY,Song WY,et al.Factors influencing matrix effects of sabarubicin and its major metabolite in human plasma during liquid chromatography-tandem mass spectrometry analysis[J].Chin J New Drug(中国新药杂志),2016,25(11):1241-1247.
[19]Barri T,Dragsted LO.UPLC-ESI-QTOF/MS and multivariate data analysis for blood plasma and serum metabolomics:effect of experimental artefacts and anticoagulant[J].Anal Chim Acta,2013,768:118-128.
[20]Rao Z,Qin HY,Shao YY,et al.Determination of serotonin concentration in rat plasma by LC-MS/MS with pre-column derivatization[J].J Chin Hosp Pharm(中国医院药学杂志),2015,35(20):1811-1815.
[21]Timms JF,Arslan-Low E,Gentry-Maharaj A,et al.Preanalytic influence of sample handling on SELDI-TOF serum protein profiles[J].Clin Chem,2007,53(4):645-656.
[22]Hirayama A,Sugimoto M,Suzuki A,et al.Effects of processing and storage conditions on charged metabolomic profiles in blood[J].Electrophoresis,2015,36(18):2148-2155.
[23]Jrgenrud B,Jntti S,Mattila I,et al.The influence of sample collection methodology and sample preprocessing on the blood metabolic profle[J].Bioanalysis,2015,7(8):991-1006.
[24]Yu ZH,Kastenmüller G,He Y,et al.Differences between human plasma and serum metabolite profiles[J].Plos One,2011,6(7):e21230.
[25]Yin P,Peter A,Franken H,et al.Preanalytical aspects and sample quality assessment in metabolomics studies of human blood[J].Clin Chem,2013,59(5):833-845.
[26]Trezzi JP,Jger C,Galozzi S,et al.Metabolic profiling of body fluids and multivariate data analysis[J].MethodsX,2017,4:95-103.
[27]Zivkovic AM,Wiest MM,Nguyen UT,et al.Effects of sample handling and storage on quantitative lipid analysis in human serum[J].Metabolomics,2009,5(4):507-516.
[28]Mischak H,Apweiler R,Banks RE,et al.Clinical proteomics:A need to define the field and to begin to set adequate standards[J].Proteomics Clin Appl,2007,1(2):148-156.
[29]Want EJ,Wilson ID,Gika H,et al.Global metabolic profiling procedures for urine using UPLC-MS[J].Nature Protocols,2010,5(6):1005-1018.
[30]Siddiqui NY,DuBois LG,John-Williams LS,et al.Optimizing urine processing protocols for protein and metabolite detection[J].J Proteomics Bioinform,2015,2015(Suppl 14):1-17.
[31]Bernini P,Bertini I,Luchinat C,et al.Standard operating procedures for pre-analytical handling of blood and urine for metabolomic studies and biobanks[J].J Biomol NMR,2011,49(3-4):231-243.
[32]Yuille M,Illig T,Hveem K,et al.Laboratory management of samples in biobanks:European consensus expert group report[J].Biopreserv Biobank,2010,8(1):65-69.
[33]Gika HG,Zisi C,Theodoridis G,et al.Protocol for quality control in metabolic profiling of biological fluids by U(H)PLC-MS[J].J Chromatogr B Analyt Technol Biomed Life Sci,2016,1008:15-25.
[34]Wang Y,Caldwell R,Cowan DA,et al.LC-MS-based metabolomics discovers purine endogenous associations with low-dose salbutamol in urine collected for antidoping tests[J].Anal Chem,2016,88(4):2243-2249.
[35]Khamis MM,Adamko DJ,El-Aneed A.Mass spectrometric based approaches in urine metabolomics and biomarker discovery[J].Mass Spectrom Rev,2017,36(2):115-134.
[36]Emwas AH,Al-Talla ZA,Kharbatia NM.Sample collection and preparation of biofluids and extracts for gas chromatography-mass spectrometry[J].Methods Mol Biol,2015,1277:75-90.
[37]Emwas AH,Roy R,McKay RT,et al.Recommendations and standardization of biomarker quantification using NMR-based metabolomics with particular focus on urinary analysis[J].JProteome Res,2016,15(2):360-373.
[38]Saude EJ,Sykes BD.Urine stability for metabolomic studies:effects of preparation and storage[J].Metabolomics,2007,3(1):19-27.
[39]Gika HG,Theodoridis GA,Wilson ID.Liquid chromatography and ultra-performance liquid chromatography-mass spectrometry fingerprinting of human urine:sample stability under different handling and storage conditions for metabonomics studies[J].J Chromatogr A,2008,1189(1-2):314-322.
[40]Vuckovic D.Current trends and challenges in sample preparation for global metabolomics using liquid chromatographymass spectrometry[J].Anal Bioanal Chem,2012,403(6):1523-1548.