Liquid Chromatography Mass Spectrometry Bioanalysis of Protein Therapeutics and Biomarkers in Biological Matrices
Fumin Li
Bioanalytical Department, Covance Laboratories, Madison, Wisconsin, USA
Search for more papers by this authorQin C. Ji
Bioanalytical Sciences, Analytical Research & Development, Bristol-Myers Squibb, Princeton, New Jersey, USA
Search for more papers by this authorFumin Li
Bioanalytical Department, Covance Laboratories, Madison, Wisconsin, USA
Search for more papers by this authorQin C. Ji
Bioanalytical Sciences, Analytical Research & Development, Bristol-Myers Squibb, Princeton, New Jersey, USA
Search for more papers by this authorMingshe Zhu
Department of Biotransformation, Bristol-Myers Squibb Research and Development, Princeton, New Jersey, USA
Search for more papers by this authorSummary
This chapter contains sections titled:
-
General Introduction
-
Protein Quantitation by LC–MS/MS
-
Protein Quantitation Using Intact Proteins by LC–MS/MS
-
Protein Quantitation Using Representative Peptides by LC–MS/MS
-
Consideration of Internal Standard for Protein Quantitation
-
Matrix Effect, Matrix Suppression/Enhancement, and Recovery
-
Sensitivity Enhancement via Immunocapture/Purification
-
Sensitivity Enhancement via Depletion of Abundant Proteins
-
Practical Aspects of LC–MS Assay for Proteins in Drug Development
-
Conclusions
-
Acknowledgments
-
References
REFERENCES
- Ackermann BL, Berna MJ, Eckstein JA, Ott LW, Chaudhary AK. Current applications of liquid chromatography/mass spectrometry in pharmaceutical discovery after a decade of innovation. Annu Rev Anal Chem 2008; 1: 357–396.
- Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature 2003; 422 (6928): 198–207.
- Anderson L, Hunter CL. Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol Cell Proteomics 2006: 5(4): 573–588.
- Anderson NL, Anderson NG. The human plasma proteome: History, character, and diagnostic prospects. Mol Cell Proteomics 2002: 1(11): 845–867.
- Arsene CG, Ohlendorf R, Burkitt W, Pritchard C, Henrion A, O'Connor G, Bunk DM, Güttler B. Protein quantification by isotope dilution mass spectrometry of proteolytic fragments: Cleavage rate and accuracy. Anal Chem 2008: 80(11): 4154–4160.
- Barnidge DR, Goodmanson MK, Klee GG, Muddiman DC. Absolute quantification of the model biomarker prostate-specific antigen in serum by LC-MS/MS using protein cleavage and isotope dilution mass spectrometry. J Proteome Res 2004: 3(3): 644–652.
- Barr JR, Maggio VL, Patterson DG Jr, Cooper GR, Henderson LO, Turner WE, Smith SJ, Hannon WH, Needham LL, Sampson EJ. Isotope dilution—Mass spectrometric quantification of specific proteins: Model application with apolipoprotein A-I. Clin Chem 1996: 42(10): 1676–1682.
- Beardsley RL, Reilly JP. Quantitation using enhanced signal tags: A technique for comparative proteomics. J Proteome Res 2003: 2(1): 15–21.
- Becher F, Pruvost A, Clement G, Tabet JC, Ezan E. Quantification of small therapeutic proteins in plasma by liquid chromatography–tandem mass spectrometry: Application to an elastase inhibitor EPI-hNE4. Anal Chem 2006: 78(7): 2306–2313.
- Berna M, Ackermann B. Increased throughput for low-abundance protein biomarker verification by liquid chromatography/tandem mass spectrometry. Anal Chem 2009: 81(10): 3950–3956.
- Berna MJ, Zhen Y, Watson DE, Hale JE, Ackermann BL. Strategic use of immuno-precipitation and LC/MS/MS for trace-level protein quantification: Myosin light chain 1, a biomarker of cardiac necrosis. Anal Chem 2007: 79(11): 4199–4205.
- Björhall K, Miliotis T, Davidsson P. Comparison of different depletion strategies for improved resolution in proteomic analysis of human serum samples. Proteomics 2005: 5(1): 307–317.
- Bodovitz S, Joos T. The proteomics bottleneck: Strategies for preliminary validation of potential biomarkers and drug targets. Trends Biotechnol 2004: 22(1): 4–7.
- Brönstrup M. Absolute quantification strategies in proteomics based on mass spectrometry. Expert Rev Proteomics 2004: 1(4): 503–512.
- Careri M, Mangia A. Analysis of food proteins and peptides by chromatography and mass spectrometry. J Chromatogr A 2003; 1000(1–2): 609–635.
- Cho SY, Lee EY, Lee JS, Kim HY, Park JM, Kwon MS, Park YK, Lee HJ, Kang MJ, Kim JY, Yoo JS, Park SJ, Cho JW, Kim HS, Paik YK. Efficient prefractionation of low-abundance proteins in human plasma and construction of a two-dimensional map. Proteomics 2005: 5(13): 3386–3396.
- Chromy BA, Gonzales AD, Perkins J, Choi MW, Corzett MH, Chang BC, Corzett CH, McCutchen-Maloney SL. Proteomic analysis of human serum by two-dimensional differential gel electrophoresis after depletion of high-abundant proteins. J Proteome Res 2004: 3(6): 1120–1127.
- Czerwenka C, Maier I, Potocnik N, Pittner F, Lindner W. Absolute quantitation of beta-lactoglobulin by protein liquid chromatography–mass spectrometry and its application to different milk products. Anal Chem 2007: 79(14): 5165–5172.
- De Hoffman E, Charette J, Stroobant V. Mass Spectrometrys Principles and Applications, 2nd ed. Wiley, New York, 2001.
- DeSilva B, Smith W, Weiner R, Kelley M, Smolec J, Lee B, Khan M, Tacey R, Hill H, Celniker A. Recommendations for the bioanalytical method validation of ligand-binding assays to support pharmacokinetic assessments of macromolecules. Pharm Res 2003: 20(11): 1885–1900.
- Dubois M, Fenaille F, Clement G, Lechmann M, Tabet JC, Ezan E, Becher F. Immunopurification and mass spectrometric quantification of the active form of a chimeric therapeutic antibody in human serum. Anal Chem 2008: 80(5): 1737–1745.
- Echan LA, Tang HY, Ali-Khan N, Lee K, Speicher DW. Depletion of multiple high-abundance proteins improves protein profiling capacities of human serum and plasma. Proteomics 2005: 5(13): 3292–3303.
- Elliott MH, Smith DS, Parker CE, Borchers C. Current trends in quantitative proteomics. J Mass Spectrom 2009: 44(12): 1637–1660.
- Food and Drug Administration (FDA). Guidance for Industry-Bioanalytical Method Validation; U.S. Department of Health and Human Services, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM), May 2000, available: http://www.fda.gov/cder/guidance/index.htm.
- Gerber SA, Kettenbach AN, Rush J, Gygi SP. The absolute quantification strategy: Application to phosphorylation profiling of human separase serine 1126. Methods Mol Biol 2007; 359: 71–86.
- Gianazza E, Arnaud P. Chromatography of plasma proteins on immobilized Cibacron Blue F3-GA. Mechanism of the molecular interaction. Biochem J 1982; 203 (3): 637–641.
- Goshe MB, Veenstra TD, Panisko EA, Conrads TP, Angell NH, Smith RD. Phospho-protein isotope-coded affinity tags: Application to the enrichment and identification of low-abundance phosphoproteins. Anal Chem 2002: 74(3): 607–616.
- Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 1999: 17(10): 994–999.
- Hagman C, Ricke D, Ewert S, Bek S, Falchetto R, Bitsch F. Absolute quantification of monoclonal antibodies in biofluids by liquid chromatography–tandem mass spectrometry. Anal Chem 2008: 80(4): 1290–1296.
- Heudi O, Barteau S, Zimmer D, Schmidt J, Bill K, Lehmann N, Bauer C, Kretz O. Towards absolute quantification of therapeutic monoclonal antibody in serum by LC-MS/MS using isotope-labeled antibody standard and protein cleavage isotope dilution mass spectrometry. Anal Chem 2008; 80(11): 4200–4207.
- Hoofnagle AN, Wener MH. The fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry. J Immunol Methods 2009; 347(1–2): 3–11.
- Jemal M, Ouyang Z, Xia YQ. Systematic LC-MS/MS bioanalytical method development that incorporates plasma phospholipids risk avoidance, usage of incurred sample and well thought-out chromatography. Biomed Chromatogr 2010; 24: 2–19.
- Jemal M, Xia YQ. LC-MS development strategies for quantitative bioanalysis. Curr Drug Metab 2006: 7(5): 491–502.
- Ji C, Li W, Ren XD, El-Kattan AF, Kozak R, Fountain S, Lepsy C. Diethylation labeling combined with UPLC/MS/MS for simultaneous determination of a panel of monoamine neurotransmitters in rat prefrontal cortex microdialysates. Anal Chem 2008: 80(23): 9195–9203.
- Ji C, Sadagopan N, Zhang Y, Lepsy C. A universal strategy for development of a method for absolute quantification of therapeutic monoclonal antibodies in biological matrices using differential dimethyl labeling coupled with ultra performance liquid chromatography–tandem mass spectrometry. Anal Chem 2009: 81(22): 9321–9328.
- Ji QC, Rodila R, El-Shourbagy TA. A sample preparation process for LC-MS/MS analysis of total protein drug concentrations in monkey plasma samples with antibody. J Chromatogr B Analyt Technol Biomed Life Sci. 2007: 847(2): 133–141.
- Ji QC, Rodila R, Gage EM, El-Shourbagy TA. A strategy of plasma protein quantitation by selective reaction monitoring of an intact protein. Anal Chem 2003; 75(24): 7008–7014.
- Ji QC, Rodila R, Gage EM, El-Shourbagy TA. Mass spectrometric approaches for protein quantitation in drug development. Am Pharm Rev 2004: 7(3): 84–89.
- Ji QC, Rodila R, Morgan SJ, Humerickhouse RA, El-Shourbagy TA. Investigation of the immunogenicity of a protein drug using equilibrium dialysis and liquid chromatography tandem mass spectrometry detection. Anal Chem 2005: 77(17): 5529–5533.
- John H, Walden M, Schäfer S, Genz S, Forssmann WG. Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography–mass spectrometry. Anal Bioanal Chem 2004: 378(4): 883–897.
- Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 1986; 321: 522–525.
- Kay RG, Gregory B, Grace PB, Pleasance S. The application of ultra-performance liquid chromatography/tandem mass spectrometry to the detection and quantitation of apolipoproteins in human serum. Rapid Commun Mass Spectrom 2007: 21(16): 2585–2593.
- Kippen AD, Cerini F, Vadas L, Stöcklin R, Vu L, Offord RE, Rose K. Development of an isotope dilution assay for precise determination of insulin, C-peptide, and proinsulin levels in non-diabetic and type II diabetic individuals with comparison to immunoassay. J Biol Chem 1997: 272(19): 12513–12522.
- Kirkpatrick DS, Gerber SA, Gygi SP. The absolute quantification strategy: A general procedure for the quantification of proteins and post-translational modifications. Methods 2005: 35(3): 265–273.
- Kuhn E, Wu J, Karl J, Liao H, Zolg W, Guild B. Quantification of C-reactive protein in the serum of patients with rheumatoid arthritis using multiple reaction monitoring mass spectrometry and 13C-labeled peptide standards. Proteomics 2004: 4(4): 1175–1186.
- Leader B, Baca QJ, Golan, DE. Protein therapeutics: A summary and pharmacological classification. Nat Rev Drug Discov 2008; 7: 21–39.
- Lee MS. Strategies for Drug Discovery Using Mass Spectrometry. Wiley, Hoboken, NJ, 2006.
- Li F, Schmerberg CM, Ji QC. Accelerated tryptic digestion of proteins in plasma for absolute quantitation using a protein internal standard by liquid chromatography/ tandem mass spectrometry. Rapid Commun Mass Spectrom 2009: 23(5): 729–732.
- Li F, Schmerberg CM, Ji QC. Characterization of methanol assisted accelerated tryptic digestion for absolute protein quantitation in human plasma using LC-MS/MS. Manuscript in preparation.
- Lin S, Shaler TA, Becker CH. Quantification of intermediate-abundance proteins in serum by multiple reaction monitoring mass spectrometry in a single-quadrupole ion trap. Anal Chem 2006: 78(16): 5762–5767.
- Linscheid MW, Ahrends R, Pieper S, Kühn A. Liquid chromatography–mass spectrometry-based quantitative proteomics. Methods Mol Biol 2009; 564: 189–205.
- Liu T, Qian WJ, Mottaz HM, Gritsenko MA, Norbeck AD, Moore RJ, Purvine SO, Camp DG 2nd, Smith RD. Evaluation of multiprotein immunoaffinity subtraction for plasma proteomics and candidate biomarker discovery using mass spectrometry. Mol Cell Proteomics 2006: 5(11): 2167–2174.
- Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 2004: 93(11): 2645–2668.
- Mascelli MA, Zhou H, Sweet R, Getsy J, Davis HM, Graham M, Abernethy D. Molecular, biologic, and pharmacokinetic properties of monoclonal antibodies: Impact of these parameters on early clinical development. J Clin Pharmacol 2007; 47: 553–565.
- Mayr BM, Kohlbacher O, Reinert K, Sturm M, Gröpl C, Lange E, Klein C, Huber CG. Absolute myoglobin quantitation in serum by combining two-dimensional liquid chromatography–electrospray ionization mass spectrometry and novel data analysis algorithms. J Proteome Res 2006: 5(2): 414–421.
- Motoyama A, Yates JR 3rd. Multidimensional LC separations in shotgun proteomics. Anal Chem 2008: 80(19): 7187–7193.
- Münchbach M, Quadroni M, Miotto G, James P. Quantitation and facilitated de novo sequencing of proteins by isotopic N-terminal labeling of peptides with a fragmentation-directing moiety. Anal Chem 2000: 72(17): 4047–4057.
- Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol 2005: 1(5): 252–262.
- Prestera T, Prochaska HJ, Talalay P. Inhibition of NAD(P)H:(quinone-acceptor) oxidoreductase by cibacron blue and related anthraquinone dyes: A structure-activity study. Biochemistry 1992: 31(3): 824–833.
- Qiu Y, Sousa EA, Hewick RM, Wang JH. Acid-labile isotope-coded extractants: A class of reagents for quantitative mass spectrometric analysis of complex protein mixtures. Anal Chem 2002: 74(19): 4969–4979.
- Ramström M, Hagman C, Mitchell JK, Derrick PJ, Håkansson P, Bergquist J. Depletion of high-abundant proteins in body fluids prior to liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry. J Proteome Res 2005; (2): 410–416.
- Russell WK, Park ZY, Russell DH. Proteolysis in mixed organic-aqueous solvent systems: Applications for peptide mass mapping using mass spectrometry. Anal Chem 2001; 73(11): 2682–2685.
- Shores KS, Knapp DR. Assessment approach for evaluating high abundance protein depletion methods for cerebrospinal fluid (CSF) proteomic analysis. J Proteome Res 2007: 6(9): 3739–3751.
- Taylor PJ. Matrix effects: The Achilles heel of quantitative high-performance liquid chromatography–electrospray–tandem mass spectrometry. Clin Biochem 2005; 38(4): 328–334.
- Thresher WC, Swaisgood HE. Characterization of specific interactions of coenzymes, regulatory nucleotides and cibacron blue with nucleotide binding domains of enzymes by analytical affinity chromatography. J Mol Recognit 1990; 3(5–6): 220–228.
- Tubbs KA, Kiernan UA, Niederkofler EE, Nedelkov D, Bieber AL, Nelson RW. Development of recombinant-based mass spectrometric immunoassay with application to resistin expression profiling. Anal Chem 2006: 78(10): 3271–3276.
- Van den Broek I, Sparidans RW, Schellens JH, Beijnen JH. Quantitative bioanalysis of peptides by liquid chromatography coupled to (tandem) mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 872(1–2): 1–22.
- Volosov A, Napoli KL, Soldin SJ. Simultaneous simple and fast quantification of three major immunosuppressants by liquid chromatography–tandem mass-spectrometry. Clin Biochem 2001: 34(4): 285–290.
- Weiner LM. Fully human therapeutic monoclonal antibodies. J Immunother 2006; 29(1): 1–9.
- Whiteaker JR, Zhao L, Zhang HY, Feng LC, Piening BD, Anderson L, Paulovich AG. Antibody-based enrichment of peptides on magnetic beads for mass-spectrometry-based quantification of serum biomarkers. Anal Biochem 2007: 362(1): 44–54.
- Yang Z, Hayes M, Fang X, Daley MP, Ettenberg S, Tse FL. LC-MS/MS approach for quantification of therapeutic proteins in plasma using a protein internal standard and 2D-solid-phase extraction cleanup. Anal Chem 2007: 79(24): 9294–9301.
- Yang Z, Ke J, Hayes M, Bryant M, Tse FL. A sensitive and high-throughput LC-MS/ MS method for the quantification of pegylated-interferon-alpha2a in human serum using monolithic C18 solid phase extraction for enrichment. J Chromatogr B Analyt Technol Biomed Life Sci 2009; 877(18–19): 1737–1742.
- Yates JR, Ruse CI, Nakorchevsky A. Proteomics by mass spectrometry: approaches, advances, and applications. Annu Rev Biomed Eng 2009; 11: 49–79.