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Key Mass Spectrometry Techniques Used in Clinical Biomarker Research

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Translating Molecular Biomarkers into Clinical Assays

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 21))

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Abstract

Mass spectrometry has been playing an increasingly important role in various aspects of biomarker research, ranging from discovery of novel biomarkers to quantitative measurement of known biomarkers for clinical applications. Following a brief overview of multiple reaction monitoring (MRM)-based LC/MS approach, the gold standard for quantitative mass spectrometry, this chapter provides an overview of several emerging mass spectrometry techniques benefit from recent advances in mass spectrometry instrumentation and related technologies. These new techniques enable researchers to develop sensitive, specific, robust, and higher throughput biomarker assays for novel clinical applications. Multiple reaction monitoring cubed (MRM3) technique is capable of measuring analytes in complex matrices without extensive sample pretreatment. High-pressure, high-resolution separations with intelligent selection and multiplexing (PRISM) technique greatly increase the efficiency of complex sample analysis in a highly automatic fashion. High-resolution mass spectrometry (HRMS) enables the extraction of analyte information from complicated matrices with minimal efforts in method development. Parallel reaction monitoring (PRM) offers an enhanced MRM approach with better tolerance to background interference and the potential of achieving better detection limits. Microfluidic LC/MS utilizes low-flow LC to boost sensitivity tremendously and enables the detection of extremely low-abundance analytes. Stable isotope dilution mass spectrometry (SID-MS) enables accurate measurement of protein and peptide in biological matrices. These new technologies have changed the landscape of MS usage in clinical biomarker field and will continue to bring positive impact as more advanced tools become available.

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References

  1. Smith RD (2012) Mass spectrometry in biomarker applications: from untargeted discovery to targeted verification, and implications for platform convergence and clinical application. Clin Chem 58:528–530

    Article  CAS  PubMed  Google Scholar 

  2. Grebe SKG, Singh RJ (2011) LC-MS/MS in the clinical laboratory-where to from here? Clin Biochem Rev 21:5–31

    Google Scholar 

  3. Kitteringham NR, Jenkins RE, Lane CS, Elliott VL, Park BK (2009) Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics. J Chromatogr B 877:1229–1239

    Article  CAS  Google Scholar 

  4. Fortin T, Salvador A, Charrier JP, Lenz C, Bettsworth F, Lacoux X, Choquet-Kastylevsky G, Lemonine J (2009) Multiple reaction monitoring cubed for protein quantification at low nanogram/milliliter level in nondepleted human serum. Anal Chem 81:9343–9352

    Article  CAS  PubMed  Google Scholar 

  5. Jaffuel A, Lemonine J, Aubert C, Simon R, Leonard J-F, Gautier J-C, Pasquier O, Salvador A (2013) Optimization of liquid chromatography-multiple reaction monitoring cubed mass spectrometry assay for protein quantification: application to aquaporin-2 water channel in human urine. J Chromatogr A 1301:122–130

    Article  CAS  PubMed  Google Scholar 

  6. Shi T, Fillmore TL, Sun X, Zhao R, Schepmoes AA, Hossain M. Xie F, Wu S, Kim J-s, Jone N. Moore RJ, Pasa-Tolic L, Kagan J, Rodland KD, Liu T, Tang K, Camp DG, Smith RD, Qian W-J (2012) Antibody-free, targeted mass-spectrometric approach for quantification of protein at low pictogram per milliliter levels in human plasma/serum. PNAS 190:15395–15400

    Google Scholar 

  7. Shi T, Sun X, Gao Y, Fillmore TL, Schepmoes AA, Zhao R, He J, Moore RJ, Kagan J, Rodland KD, Liu T, Liu AY, Smith RD, Tang K, Camp DG, Qian W-J (2013) Targeted quantification of low ng/mL level proteins in human serum without immunoaffinity depletion. J Proteome Res 12:3353–3361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rochat B, Kottelat E, McMullen J. The future key role of LC-high-resolution-MS analyses in clinical laboratories: a focus on quantitation. Bioanalysis 4:2939–2958

    Google Scholar 

  9. Goodenough A (2011) High resolution mass spectrometry approaches for the quantification of proteins using stable isotopically labeled peptide, 21–30 May/June 2011

    Google Scholar 

  10. Peterson AC, Russell JD, Bailey DJ, Westphall MS, Coon JJ (2012) Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Mol Cell Proteomics 11:1475–1488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Arnold DW, Needhma SR (2013) Micro-LC-MS/MS: the future of bioanalysis. Bioanalysis 5(11):1329–1331

    Article  CAS  PubMed  Google Scholar 

  12. Christianson CC, Johnson CJL, Needham SR (2013) The advantages of microflow LC-MS/MS compared with conventional HPLC-MS/MS for the analysis of methotrexate from human plasma. Bioanalysis 5(11):1387–1396

    Article  CAS  PubMed  Google Scholar 

  13. Zhu KY, Leung KW, Ting AKL, Wong ZCF, Ng WYY, Choi RCY, Dong TTX, Wang T, Lau DTW, Tsim KWT (2012) Microfluidic chip based nano liquid chromatography coupled to tandem mass spectrometry for the determination of abused drugs and metabolites in human hair. Anal Bioanal Chem 402:2805–2815

    Article  CAS  PubMed  Google Scholar 

  14. Broccardo CJ, Schauer KL, Kohrt WM, Schwartz RS, Murphy JP, Prenni JE (2013) Multiplexed analysis of steroid hormones in human serum using novel microflow tile technology and LC-MS/MS. J Chromatogr B 934:16–21

    Article  CAS  Google Scholar 

  15. Lee MS, Kerns EH (1999) LC/MS applications in drug development. Mass Spectrom Rev 18:187–279

    Article  CAS  PubMed  Google Scholar 

  16. Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA (2010) Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 6:2212–2229

    Article  CAS  Google Scholar 

  17. Kuhn E, Addona T, Keshishian H, Burgass M, Mani DR, Lee RT, Sabatine MS, Gerszten RE, Carr SA (2009) Developing multiplexed assays for troponin I and interleukin-33 in plasma by peptide immunoaffinity enrichment and targeted mass spectrometry. Clin Chem 55:1108–1117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Whiteaker JR, Zhao L, Anderson L, Paulovich AG (2010) An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers. Mol Cell Proteomics 9:184–196

    Article  CAS  PubMed  Google Scholar 

  19. Kuhn E, Whiteaker JR, Mani DR, Jackson AM, Zhao L, Pope ME, Smith E, Rivera KD, Anderson NL, Skates SJ, Pearson TW, Paulovich AG, Carr SA (2012) Interlaboratory evaluation of automated, multiplexed peptide immunoaffinity enrichment coupled to multiple reaction monitoring mass spectrometry for quantifying proteins in plasma. Mol Cell Proteomics 11:1–14

    Article  CAS  Google Scholar 

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Correspondence to Mingxiang Lin .

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Lin, M. (2016). Key Mass Spectrometry Techniques Used in Clinical Biomarker Research. In: Weiner, R., Kelley, M. (eds) Translating Molecular Biomarkers into Clinical Assays . AAPS Advances in the Pharmaceutical Sciences Series, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-319-40793-7_14

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