References
- Houde D, Peng Y, Berkowitz SA, Engen JR. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Molecul Cell Proteomics. 2010;9:1716. doi:https://doi.org/10.1074/mcp.M900540-MCP200.
- Vlasak J, Bussat MC, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, Kirchmeier M, Corvaïa N, Ionescu R, Beck A. Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Anal Biochem. 2009;392:145–12. doi:https://doi.org/10.1016/j.ab.2009.05.043.
- Talebi M, Nordborg A, Gaspar A, Lacher NA, Wang Q, He XZ, Haddad PR, Hilder EF. Charge heterogeneity profiling of monoclonal antibodies using low ionic strength ion-exchange chromatography and well-controlled pH gradients on monolithic columns. J Chromatogr A. 2013;1317:148–54. doi:https://doi.org/10.1016/j.chroma.2013.08.061.
- Neill A, Nowak C, Patel R, Ponniah G, Gonzalez N, Miano D, Liu H. Characterization of recombinant monoclonal antibody charge variants using OFFGEL fractionation, weak anion exchange chromatography, and mass spectrometry. Anal Chem. 2015;87:6204–11. doi:https://doi.org/10.1021/acs.analchem.5b01452.
- Vlasak J, Ionescu R. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods. Curr Pharm Biotechnol. 2008;9:468–81. doi:https://doi.org/10.2174/138920108786786402.
- Gandhi S, Ren D, Xiao G, Bondarenko P, Sloey C, Ricci MS, Krishnan S. Elucidation of degradants in acidic peak of cation exchange chromatography in an IgG1 monoclonal antibody formed on long-term storage in a liquid formulation. Pharm Res. 2012;29:209–24. doi:https://doi.org/10.1007/s11095-011-0536-0.
- Chen XN, Nguyen M, Jacobson F, Ouyang J. Charge-based analysis of antibodies with engineered cysteines: from multiple peaks to a single main peak. MAbs. 2009;1:563–71. doi:https://doi.org/10.4161/mabs.1.6.10058.
- Perkins M, Theiler R, Lunte S, Jeschke M. Determination of the origin of charge heterogeneity in a murine monoclonal antibody. Pharm Res. 2000;17:1110–17. doi:https://doi.org/10.1023/A:1026461830617.
- Chumsae C, Gifford K, Lian W, Liu H, Radziejewski CH, Zhou ZS. Arginine modifications by methylglyoxal: discovery in a recombinant monoclonal antibody and contribution to acidic species. Anal Chem. 2013;85:11401–09. doi:https://doi.org/10.1021/ac402384y.
- Griaud F, Denefeld B, Lang M, Hensinger H, Haberl P, Berg M. Unbiased in-depth characterization of CEX fractions from a stressed monoclonal antibody by mass spectrometry. mAbs. 2017;9:820–30. doi:https://doi.org/10.1080/19420862.2017.1313367.
- Alvarez M, Tremintin G, Wang J, Eng M, Y-H K, Jeong J, Ling VT, Borisov OV. On-line characterization of monoclonal antibody variants by liquid chromatography–mass spectrometry operating in a two-dimensional format. Anal Biochem. 2011;419:17–25. doi:https://doi.org/10.1016/j.ab.2011.07.033.
- Pristatsky P, Cohen SL, Krantz D, Acevedo J, Ionescu R, Vlasak J. Evidence for trisulfide bonds in a recombinant variant of a human IgG2 monoclonal antibody. Anal Chem. 2009;81:6148–55. doi:https://doi.org/10.1021/ac9006254.
- Battersby JE, Snedecor B, Chen C, Champion KM, Riddle L, Vanderlaan M. Affinity–reversed-phase liquid chromatography assay to quantitate recombinant antibodies and antibody fragments in fermentation broth. J Chromatogr A. 2001;927:61–76. doi:https://doi.org/10.1016/S0021-9673(01)01108-6.
- Beck A, Bussat M-C, Zorn N, Robillard V, Klinguer-Hamour C, Chenu S, Goetsch L, Corvaïa N, Van Dorsselaer A, Haeuw J-F. Characterization by liquid chromatography combined with mass spectrometry of monoclonal anti-IGF-1 receptor antibodies produced in CHO and NS0 cells. J Chromatogr B. 2005;819:203–18. doi:https://doi.org/10.1016/j.jchromb.2004.06.052.
- Johnson KA, Paisley-Flango K, Tangarone BS, Porter TJ, Rouse JC. Cation exchange–HPLC and mass spectrometry reveal C-terminal amidation of an IgG1 heavy chain. Anal Biochem. 2007;360:75–83. doi:https://doi.org/10.1016/j.ab.2006.10.012.
- Sreedhara A, Cordoba A, Zhu Q, Kwong J, Liu J. Characterization of the isomerization products of aspartate residues at two different sites in a monoclonal antibody. Pharm Res. 2012;29:187–97. doi:https://doi.org/10.1007/s11095-011-0534-2.
- Xiao G, Bondarenko PV, Jacob J, Chu GC, Chelius D. 18O labeling method for identification and quantification of succinimide in proteins. Anal Chem. 2007;79:2714–21. doi:https://doi.org/10.1021/ac0617870.
- Chu GC, Chelius D, Xiao G, Khor HK, Coulibaly S, Bondarenko PV. Accumulation of succinimide in a recombinant monoclonal antibody in mildly acidic buffers under elevated temperatures. Pharm Res. 2007;24:1145–56. doi:https://doi.org/10.1007/s11095-007-9241-4.
- Liu H, Ponniah G, Zhang H-M, Nowak C, Neill A, Gonzalez-Lopez N, Patel R, Cheng G, Kita AZ, Andrien B. In vitro and in vivo modifications of recombinant and human IgG antibodies. mAbs. 2014;6:1145–54. doi:https://doi.org/10.4161/mabs.29883.
- Berkowitz SA, Engen JR, Mazzeo JR, Jones GB. Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars. Nat Rev Drug Discovery. 2012;11:527. doi:https://doi.org/10.1038/nrd3746.
- Kang X, Kutzko JP, Hayes ML, Frey DD. Monoclonal antibody heterogeneity analysis and deamidation monitoring with high-performance cation-exchange chromatofocusing using simple, two component buffer systems. J Chromatogr A. 2013;1283:89–97. doi:https://doi.org/10.1016/j.chroma.2013.01.101.
- Farsang E, Murisier A, Horváth K, Beck A, Kormány R, Guillarme D, Fekete S. Tuning selectivity in cation-exchange chromatography applied for monoclonal antibody separations, part 1: alternative mobile phases and fine tuning of the separation. J Pharm Biomed Anal. 2019;168:138–47. doi:https://doi.org/10.1016/j.jpba.2019.02.024.
- Trappe A, Fussl F, Carillo S, Zaborowska I, Meleady P, Bones J. Rapid charge variant analysis of monoclonal antibodies to support lead candidate biopharmaceutical development. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1095:166–76. doi:https://doi.org/10.1016/j.jchromb.2018.07.037.
- Sankaran PK, Kabadi PG, Honnappa CG, Subbarao M, Pai HV, Adhikary L, Palanivelu DV. Identification and quantification of product-related quality attributes in bio-therapeutic monoclonal antibody via a simple, and robust cation-exchange HPLC method compatible with direct online detection of UV and native ESI-QTOF-MS analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1102–1103:83–95. doi:https://doi.org/10.1016/j.jchromb.2018.10.019.
- Sandra K, Steenbeke M, Vandenheede I, Vanhoenacker G, Sandra P. The versatility of heart-cutting and comprehensive two-dimensional liquid chromatography in monoclonal antibody clone selection. J Chromatogr A. 2017;1523:283–92. doi:https://doi.org/10.1016/j.chroma.2017.06.052.
- Zhang H, Cui W, Gross ML. Mass spectrometry for the biophysical characterization of therapeutic monoclonal antibodies. FEBS Lett. 2014;588:308–17. doi:https://doi.org/10.1016/j.febslet.2013.11.027.
- Stoll DR, Harmes DC, Danforth J, Wagner E, Guillarme D, Fekete S, Beck A. Direct identification of rituximab main isoforms and subunit analysis by online selective comprehensive two-dimensional liquid chromatography–mass spectrometry. Anal Chem. 2015;87:8307–15. doi:https://doi.org/10.1021/acs.analchem.5b01578.
- Sorensen M, Harmes DC, Stoll DR, Staples GO, Fekete S, Guillarme D, Beck A. Comparison of originator and biosimilar therapeutic monoclonal antibodies using comprehensive two-dimensional liquid chromatography coupled with time-of-flight mass spectrometry. mAbs. 2016;8:1224–34. doi:https://doi.org/10.1080/19420862.2016.1203497.
- Fussl F, Cook K, Scheffler K, Farrell A, Mittermayr S, Bones J. Charge variant analysis of monoclonal antibodies using direct coupled pH gradient cation exchange chromatography to high-resolution native mass spectrometry. Anal Chem. 2018;90:4669–76. doi:https://doi.org/10.1021/acs.analchem.7b05241.
- Miao S, Xie P, Zou M, Fan L, Liu X, Zhou Y, Zhao L, Ding D, Wang H, Tan WS. Identification of multiple sources of the acidic charge variants in an IgG1 monoclonal antibody. Appl Microbiol Biotechnol. 2017;101:5627–38. doi:https://doi.org/10.1007/s00253-017-8301-x.
- Guo J, Creasy AD, Barker G, Carta G. Surface induced three-peak elution behavior of a monoclonal antibody during cation exchange chromatography. J Chromatogr A. 2016;1474:85–94. doi:https://doi.org/10.1016/j.chroma.2016.10.061.
- Leblanc Y, Ramon C, Bihoreau N, Chevreux G. Charge variants characterization of a monoclonal antibody by ion exchange chromatography coupled on-line to native mass spectrometry: case study after a long-term storage at +5°C. J Chromatography B. 2017;1048:130–39. doi:https://doi.org/10.1016/j.jchromb.2017.02.017.
- Muneeruddin K, Nazzaro M, Kaltashov IA. Characterization of intact protein conjugates and biopharmaceuticals using ion-exchange chromatography with online detection by native electrospray ionization mass spectrometry and top-down tandem mass spectrometry. Anal Chem. 2015;87:10138–45. doi:https://doi.org/10.1021/acs.analchem.5b02982.
- Yan Y, Liu AP, Wang S, Daly TJ, Li N. Ultrasensitive characterization of charge heterogeneity of therapeutic monoclonal antibodies using strong cation exchange chromatography coupled to native mass spectrometry. Anal Chem. 2018;90:13013–20. doi:https://doi.org/10.1021/acs.analchem.8b03773.
- Bailey AO, Han G, Phung W, Gazis P, Sutton J, Josephs JL, Sandoval W. Charge variant native mass spectrometry benefits mass precision and dynamic range of monoclonal antibody intact mass analysis. MAbs. 2018;10:1214–25. doi:https://doi.org/10.1080/19420862.2018.1521131.
- Beck A, D’Atri V, Ehkirch A, Fekete S, Hernandez-Alba O, Gahoual R, Leize-Wagner E, François Y, Guillarme D, Cianférani S. Cutting-edge multi-level analytical and structural characterization of antibody-drug conjugates: present and future. Expert Rev Proteomics. 2019;16:337–62. doi:https://doi.org/10.1080/14789450.2019.1578215.
- Bondarenko PV, Second TP, Zabrouskov V, Makarov AA, Zhang Z. Mass measurement and top-down HPLC/MS analysis of intact monoclonal antibodies on a hybrid linear quadrupole ion trap-Orbitrap mass spectrometer. J Am Soc Mass Spectrom. 2009;20:1415–24. doi:https://doi.org/10.1016/j.jasms.2009.03.020.
- Zhang Z, Shah B. Characterization of variable regions of monoclonal antibodies by top-down mass spectrometry. Anal Chem. 2007;79:5723–29. doi:https://doi.org/10.1021/ac070483q.
- Chait BT. Mass spectrometry: bottom-up or top-down? Science. 2006;314:65. doi:https://doi.org/10.1126/science.1133987.
- Oyler BL, Khan MM, Smith DF, Harberts EM, Kilgour DPA, Ernst RK, Cross AS, Goodlett DR. Top down tandem mass spectrometric analysis of a chemically modified rough-type lipopolysaccharide vaccine candidate. J Am Soc Mass Spectrom. 2018;29:1221–29. doi:https://doi.org/10.1007/s13361-018-1897-y.
- Nedelkov D, Niederkofler EE, Oran PE, Peterman S, Nelson RW. Top-down mass spectrometric immunoassay for human insulin and its therapeutic analogs. J Proteomics. 2018;175:27–33. doi:https://doi.org/10.1016/j.jprot.2017.08.001.
- Fornelli L, Srzentic K, Huguet R, Mullen C, Sharma S, Zabrouskov V, Fellers RT, Durbin KR, Compton PD, Kelleher NL. Accurate sequence analysis of a monoclonal antibody by top-down and middle-down orbitrap mass spectrometry applying multiple ion activation techniques. Anal Chem. 2018;90:8421–29. doi:https://doi.org/10.1021/acs.analchem.8b00984.
- He L, Anderson LC, Barnidge DR, Murray DL, Hendrickson CL, Marshall AG. Analysis of monoclonal antibodies in human serum as a model for clinical monoclonal gammopathy by use of 21 tesla FT-ICR top-down and middle-down MS/MS. J Am Soc Mass Spectrom. 2017;28:827–38. doi:https://doi.org/10.1007/s13361-017-1602-6.
- Bogdanov B, Smith RD. Proteomics by FTICR mass spectrometry: top down and bottom up. Mass Spectrom Rev. 2005;24:168–200. doi:https://doi.org/10.1002/mas.20015.
- Dillon TM, Bondarenko PV, Speed Ricci M. Development of an analytical reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry method for characterization of recombinant antibodies. J Chromatogr A. 2004;1053:299–305. doi:https://doi.org/10.1016/S0021-9673(04)01410-4.
- Chelius D, Huff Wimer ME, Bondarenko PV. Reversed-phase liquid chromatography in-line with negative ionization electrospray mass spectrometry for the characterization of the disulfide-linkages of an immunoglobulin gamma antibody. J Am Soc Mass Spectrom. 2006;17:1590–98. doi:https://doi.org/10.1016/j.jasms.2006.07.008.
- Le JC, Bondarenko PV. Trap for MAbs: characterization of intact monoclonal antibodies using reversed-phase HPLC on-line with ion-trap mass spectrometry. J Am Soc Mass Spectrom. 2005;16:307–11. doi:https://doi.org/10.1016/j.jasms.2004.11.004.
- Zhang L, Vasicek LA, Hsieh S, Zhang S, Bateman KP, Henion J. Top-down LC-MS quantitation of intact denatured and native monoclonal antibodies in biological samples. Bioanalysis. 2018;10:1039–54. doi:https://doi.org/10.4155/bio-2017-0282.
- Srzentic K, Nagornov KO, Fornelli L, Lobas AA, Ayoub D, Kozhinov AN, Gasilova N, Menin L, Beck A, Gorshkov MV, et al. Multiplexed middle-down mass spectrometry as a method for revealing light and heavy chain connectivity in a monoclonal antibody. Anal Chem. 2018;90:12527–35. doi:https://doi.org/10.1021/acs.analchem.8b02398.
- Beck A, Debaene F, Diemer H, Wagner-Rousset E, Colas O, Van Dorsselaer A, Cianferani S. Cutting-edge mass spectrometry characterization of originator, biosimilar and biobetter antibodies. J Mass Spectrom. 2015;50:285–97. doi:https://doi.org/10.1002/jms.3554.
- Dekker L, Wu S, Vanduijn M, Tolic N, Stingl C, Zhao R, Luider T, Pasa-Tolic L. An integrated top-down and bottom-up proteomic approach to characterize the antigen-binding fragment of antibodies. Proteomics. 2014;14:1239–48. doi:https://doi.org/10.1002/pmic.201300366.
- Dillon TM, Bondarenko PV, Rehder DS, Pipes GD, Kleemann GR, Ricci MS. Optimization of a reversed-phase high-performance liquid chromatography/mass spectrometry method for characterizing recombinant antibody heterogeneity and stability. J Chromatogr A. 2006;1120:112–20. doi:https://doi.org/10.1016/j.chroma.2006.01.016.
- Konermann L, Rodriguez AD, Liu J. On the formation of highly charged gaseous ions from unfolded proteins by electrospray ionization. Anal Chem. 2012;84:6798–804. doi:https://doi.org/10.1021/ac301298g.
- Goswami D, Zhang J, Bondarenko PV, Zhang Z. MS-based conformation analysis of recombinant proteins in design, optimization and development of biopharmaceuticals. Methods. 2018;144:134–51. doi:https://doi.org/10.1016/j.ymeth.2018.04.011.
- Karnoup AS, Kuppannan K, Young SA. A novel HPLC-UV-MS method for quantitative analysis of protein glycosylation. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;859:178–91. doi:https://doi.org/10.1016/j.jchromb.2007.09.030.
- Wagner-Rousset E, Janin-Bussat MC, Colas O, Excoffier M, Ayoub D, Haeuw JF, Rilatt I, Perez M, Corvaia N, Beck A. Antibody-drug conjugate model fast characterization by LC-MS following IdeS proteolytic digestion. MAbs. 2014;6:173–84. doi:https://doi.org/10.4161/mabs.26773.
- Vanhoenacker G, Vandenheede I, David F, Sandra P, Sandra K. Comprehensive two-dimensional liquid chromatography of therapeutic monoclonal antibody digests. Anal Bioanal Chem. 2015;407:355–66. doi:https://doi.org/10.1007/s00216-014-8299-1.
- Wiggins B, Liu-Shin L, Yamaguchi H, Ratnaswamy G. Characterization of cysteine-linked conjugation profiles of immunoglobulin G1 and immunoglobulin G2 antibody-drug conjugates. J Pharm Sci. 2015;104:1362–72. doi:https://doi.org/10.1002/jps.24338.
- Harris RJ, Kabakoff B, Macchi FD, Shen FJ, Kwong M, Andya JD, Shire SJ, Bjork N, Totpal K, Chen AB. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chromatogr B Biomed Sci Appl. 2001;752:233–45. doi:https://doi.org/10.1016/S0378-4347(00)00548-X.
- Sun Y, Smith DL. Identification of disulfide-containing peptides by performic acid oxidation and mass spectrometry. Anal Biochem. 1988;172:130–38. doi:https://doi.org/10.1016/0003-2697(88)90421-6.
- Bondarenko PV, Chelius D, Shaler TA. Identification and relative quantitation of protein mixtures by enzymatic digestion followed by capillary reversed-phase liquid chromatography-tandem mass spectrometry. Anal Chem. 2002;74:4741–49. doi:https://doi.org/10.1021/ac0256991.
- Phung W, Han G, Polderdijk SGI, Dillon M, Shatz W, Liu P, Wei B, Suresh P, Fischer D, Spiess C, et al. Characterization of bispecific and mispaired IgGs by native charge-variant mass spectrometry. Int J Mass Spectrom. 2019;446:116229. doi:https://doi.org/10.1016/j.ijms.2019.116229.
- Requena JR, Dimitrova MN, Legname G, Teijeira S, Prusiner SB, Levine RL. Oxidation of methionine residues in the prion protein by hydrogen peroxide. Arch Biochem Biophys. 2004;432:188–95. doi:https://doi.org/10.1016/j.abb.2004.09.012.
- Finnegan M, Linley E, Denyer SP, McDonnell G, Simons C, Maillard J-Y. Mode of action of hydrogen peroxide and other oxidizing agents: differences between liquid and gas forms. J Antimicrob Chemother. 2010;65:2108–15. doi:https://doi.org/10.1093/jac/dkq308.
- Yang R, Jain T, Lynaugh H, Nobrega RP, Lu X, Boland T, Burnina I, T S, Caffry I, Brown M, et al. Rapid assessment of oxidation via middle-down LCMS correlates with methionine side-chain solvent-accessible surface area for 121 clinical stage monoclonal antibodies. MAbs. 2017;9:646–53. doi:https://doi.org/10.1080/19420862.2017.1290753.
- Sokolowska I, Mo J, Dong J, Lewis MJ, Hu P. Subunit mass analysis for monitoring antibody oxidation. MAbs. 2017;9:498–505. doi:https://doi.org/10.1080/19420862.2017.1279773.
- Mo J, Yan Q, So CK, Soden T, Lewis MJ, Hu P. Understanding the impact of methionine oxidation on the biological functions of IgG1 antibodies using hydrogen/deuterium exchange mass spectrometry. Anal Chem. 2016;88:9495–502. doi:https://doi.org/10.1021/acs.analchem.6b01958.
- McAuley A, Jacob J, Kolvenbach CG, Westland K, Lee HJ, Brych SR, Rehder D, Kleemann GR, Brems DN, Matsumura M. Contributions of a disulfide bond to the structure, stability, and dimerization of human IgG1 antibody CH3 domain. Protein Sci. 2008;17:95–106. doi:https://doi.org/10.1110/ps.073134408.
- Masuda K, Yamaguchi Y, Kato K, Takahashi N, Shimada I, Arata Y. Pairing of oligosaccharides in the Fc region of immunoglobulin G. FEBS Lett. 2000;473:349–57. doi:https://doi.org/10.1016/S0014-5793(00)01557-X.
- Goetze AM, Liu YD, Zhang Z, Shah B, Lee E, Bondarenko PV, Flynn GC. High-mannose glycans on the Fc region of therapeutic IgG antibodies increase serum clearance in humans. Glycobiology. 2011;21:949–59. doi:https://doi.org/10.1093/glycob/cwr027.
- Rehder DS, Chelius D, McAuley A, Dillon TM, Xiao G, Crouse-Zeineddini J, Vardanyan L, Perico N, Mukku V, Brems DN, et al. Isomerization of a single aspartyl residue of anti-epidermal growth factor receptor immunoglobulin gamma2 antibody highlights the role avidity plays in antibody activity. Biochemistry. 2008;47:2518–30. doi:https://doi.org/10.1021/bi7018223.
- Nicolardi S, Deelder AM, Palmblad M, van der Burgt YE. Structural analysis of an intact monoclonal antibody by online electrochemical reduction of disulfide bonds and fourier transform ion cyclotron resonance mass spectrometry. Anal Chem. 2014;86:5376–82. doi:https://doi.org/10.1021/ac500383c.
- Trabjerg E, Jakobsen RU, Mysling S, Christensen S, Jorgensen TJ, Rand KD. Conformational analysis of large and highly disulfide-stabilized proteins by integrating online electrochemical reduction into an optimized H/D exchange mass spectrometry workflow. Anal Chem. 2015;87:8880–88. doi:https://doi.org/10.1021/acs.analchem.5b01996.
- Folzer E, Diepold K, Bomans K, Finkler C, Schmidt R, Bulau P, Huwyler J, Mahler H-C, Koulov AV. Selective oxidation of methionine and tryptophan residues in a therapeutic IgG1 molecule. J Pharm Sci. 2015;104:2824–31. doi:https://doi.org/10.1002/jps.24509.
- Zhang Z. Large-scale identification and quantification of covalent modifications in therapeutic proteins. Anal Chem. 2009;81:8354–64. doi:https://doi.org/10.1021/ac901193n.
- Zhang Z. Prediction of collision-induced-dissociation spectra of peptides with post-translational or process-induced modifications. Anal Chem. 2011;83:8642–51. doi:https://doi.org/10.1021/ac2020917.
- Ren D, Pipes GD, Liu D, Shih LY, Nichols AC, Treuheit MJ, Brems DN, Bondarenko PV. An improved trypsin digestion method minimizes digestion-induced modifications on proteins. Anal Biochem. 2009;392:12–21. doi:https://doi.org/10.1016/j.ab.2009.05.018.