Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Back
Research Article

Rapid Development and Validation of Atoltivimab, Maftivimab and Odesivimab in Pharmaceutical Dosage form by using the RP-HPLC Method

Author(s): Pallepogu Venkateswara Rao*, Naidu Srinivasa Rao, Biswa Mohan Sahoo* and Nayaka Raghavendra Babu

Volume 20, Issue 3, 2024

Published on: 25 April, 2024

Page: [212 - 223] Pages: 12

DOI: 10.2174/0115734129300296240416070559

Price: $65

Abstract

Background: The reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed for the quantitative measurement of monoclonal antibodies (Maftivimab, Atoltivimab, and Odesivimab) in the pharmaceutical dosage form. The Food and Drug Administration (FDA) has approved these monoclonal antibodies for the treatment of Zaire ebolavirus infection in adults.

Methods: Maftivimab, Atoltivimab, and Odesivimab were separated chromatographically on the Waters Alliance-e2695 platform using the Luna Phenyl Hexyl (250 x 4.6 mm, 5 μm) column and a mobile phase made up of Acetonitrile (ACN) and ortho-phosphoric acid (OPA) buffer in a ratio of 70:30 (v/v).

Results: The flow rate was 1.0 ml/min, and a photodiode array (PDA) detector operating at room temperature was used to measure absorption at 282 nm. For Maftivimab, Atoltivimab, and Odesivimab, the theoretical plates were not less than 2000, and the tailing factor shouldn't be greater than 2, accordingly. All measurements have a constant relative standard deviation of peak areas that is less than 2.0.

Conclusion: The suggested procedure was approved following the International Conference on Harmonisation (ICH) recommendations. When used for the quantitative analysis of Maftivimab, Atoltivimab, and Odesivimab, the approach was found to be straightforward, affordable, appropriate, exact, accurate, and robust.

« Previous Next »
Graphical Abstract

[1]
Jacob, S.T.; Crozier, I.; Fischer, W.A., 2nd; Hewlett, A.; Kraft, C.S.; Vega, M.A.; Soka, M.J.; Wahl, V.; Griffiths, A.; Bollinger, L.; Kuhn, J.H. Ebola virus disease. Nat. Rev. Dis. Primers., 2020, 6(1), 13.
[http://dx.doi.org/10.1038/s41572-020-0147-3]
[2]
Leroy, E.M.; Kumulungui, B.; Pourrut, X.; Rouquet, P.; Hassanin, A.; Yaba, P.; Délicat, A.; Paweska, J.T.; Gonzalez, J.P.; Swanepoel, R. Fruit bats as reservoirs of Ebola virus. Nature, 2005, 438(7068), 575-576.
[http://dx.doi.org/10.1038/438575a] [PMID: 16319873]
[3]
Garg, R. Inmazeb: new hope for Zaire Ebola virus disease. Int. J. Basic Clin. Pharmacol., 2022, 11(3), 285-289.
[http://dx.doi.org/10.18203/2319-2003.ijbcp20221047]
[4]
Burke, J.; Ghysebrechts, S.G.; Pattyn, S.R.; Piot, P.; Ruppol, J.F.; Thonon, D. Ebola hemorrhagic fever in Zaire, 1976. Bull World Health Organ., 1978, 56(2), 271-293.
[5]
Feldman, H.; Sanchez, A.; Geisbert, W.T. Filoviridae: Marburg and ebolaviruses. In: Fields in virology; Knipe, DM; Howley, PM, Eds.; Lippincott Willams and Wilkins: Philadelphia, 2013; pp. 923-56.3.
[6]
Markham, A. REGN-EB3: First approval. Drugs, 2021, 81(1), 175-178.
[http://dx.doi.org/10.1007/s40265-020-01452-3] [PMID: 33432551]
[7]
Kamorudeen, R.T.; Adedokun, K.A.; Olarinmoye, A.O. Ebola outbreak in West Africa, 2014 – 2016: Epidemic timeline, differential diagnoses, determining factors, and lessons for future response. J. Infect. Public Health, 2020, 13(7), 956-962.
[http://dx.doi.org/10.1016/j.jiph.2020.03.014] [PMID: 32475805]
[8]
Gupta, S.; Gupta, N.; Yadav, P.; Patil, D. Ebola virus outbreak preparedness plan for developing Nations: Lessons learnt from affected countries. J. Infect. Public Health, 2021, 14(3), 293-305.
[http://dx.doi.org/10.1016/j.jiph.2020.12.030] [PMID: 33610938]
[9]
Ganiwada, B.; Tanuja, A.; Murthy, V.S.N.; Kola, P.K. Ebola-A review of threatening epidemic. Int. J. Allied Med. Sci. and Clin. Res, 2017, 5(2), 517-530.
[10]
Rhymer, W.; Speare, R. Countries’ response to WHO’s travel recommendations during the 2013–2016 Ebola outbreak. Bull. World Health Organ., 2017, 95(1), 10-17.
[http://dx.doi.org/10.2471/BLT.16.171579] [PMID: 28053360]
[11]
Nyenswah, T.G.; Kateh, F.; Bawo, L.; Massaquoi, M.; Gbanyan, M.; Fallah, M.; Nagbe, T.K.; Karsor, K.K.; Wesseh, C.S.; Sieh, S.; Gasasira, A.; Graaff, P.; Hensley, L.; Rosling, H.; Lo, T.; Pillai, S.K.; Gupta, N.; Montgomery, J.M.; Ransom, R.L.; Williams, D.; Laney, A.S.; Lindblade, K.A.; Slutsker, L.; Telfer, J.L.; Christie, A.; Mahoney, F.; De Cock, K.M. Ebola and its control in Liberia, 2014–2015. Emerg. Infect. Dis., 2016, 22(2), 169-177.
[http://dx.doi.org/10.3201/eid2202.151456] [PMID: 26811980]
[12]
Coltart, C.E.M.; Lindsey, B.; Ghinai, I.; Johnson, A.M.; Heymann, D.L. The Ebola outbreak, 2013–2016: Old lessons for new epidemics. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2017, 372(1721), 20160297.
[http://dx.doi.org/10.1098/rstb.2016.0297] [PMID: 28396469]
[13]
Fasina, F.O.; Shittu, A.; Lazarus, D.; Tomori, O.; Simonsen, L.; Viboud, C.; Chowell, G. Transmission dynamics and control of Ebola virus disease outbreak in Nigeria, July to September 2014. Euro Surveill., 2014, 19(40), 20920.
[http://dx.doi.org/10.2807/1560-7917.ES2014.19.40.20920] [PMID: 25323076]
[14]
Lu, H.J.; Qian, J.; Kargbo, D.; Zhang, X.G.; Yang, F.; Hu, Y.; Sun, Y.; Cao, Y.X.; Deng, Y.Q.; Su, H.X.; Dafae, F.; Sun, Y.; Wang, C.Y.; Nie, W.M.; Bai, C.Q.; Xia, Z.P.; Liu, K.; Kargbo, B.; Gao, G.F.; Jiang, J.F. Ebola virus outbreak investigation, Sierra Leone, September 28–November 11, 2014. Emerg. Infect. Dis., 2015, 21(11), 1921-1927.
[http://dx.doi.org/10.3201/eid2111.150582] [PMID: 26485317]
[15]
Chevalier, M.S.; Chung, W.; Smith, J.; Weil, L.M.; Hughes, S.M.; Joyner, S.N.; Hall, E.; Srinath, D.; Ritch, J.; Thathiah, P.; Threadgill, H.; Cervantes, D.; Lakey, D.L. Ebola virus disease cluster in the United States--Dallas County, Texas, 2014. MMWR Morb. Mortal. Wkly. Rep., 2014, 63(46), 1087-1088.
[PMID: 25412069]
[16]
Bertoli, G.; Mannazzu, M.; Madeddu, G.; Are, R.; Muredda, A.; Babudieri, S.; Calia, G.; Lovigu, C.; Maida, I.; Contini, L.; Miscali, A.; Rubino, S.; Delogu, F.; Mura, M.S. Ebola virus disease: Case management in the institute of infectious diseases, University Hospital of Sassari, Sardinia, Italy. J. Infect. Dev. Ctries., 2016, 10(5), 537-543.
[http://dx.doi.org/10.3855/jidc.8203] [PMID: 27249532]
[17]
Bixler, S.L.; Duplantier, A.J.; Bavari, S. Discovering drugs for the treatment of Ebola virus. Curr. Treat. Options Infect. Dis., 2017, 9(3), 299-317.
[http://dx.doi.org/10.1007/s40506-017-0130-z] [PMID: 28890666]
[18]
Chowell, G.; Nishiura, H. Transmission dynamics and control of Ebola virus disease (EVD): A review. BMC Med., 2014, 12(1), 196.
[http://dx.doi.org/10.1186/s12916-014-0196-0] [PMID: 25300956]
[19]
Mehedi, M.; Groseth, A.; Feldmann, H.; Ebihara, H. Clinical aspects of Marburg hemorrhagic fever. Future Virol., 2011, 6(9), 1091-1106.
[http://dx.doi.org/10.2217/fvl.11.79] [PMID: 22046196]
[20]
Maganga, G.D.; Kapetshi, J.; Berthet, N.; Ilunga, K.B.; Kabange, F.; Kingebeni, M.P.; Mondonge, V.; Muyembe, J.J.T.; Bertherat, E.; Briand, S.; Cabore, J.; Epelboin, A.; Formenty, P.; Kobinger, G.; Angulo, G.L.; Labouba, I.; Manuguerra, J.C.; Bele, O.J.M.; Dye, C.; Leroy, E.M. Ebola virus disease in the democratic republic of congo. N. Engl. J. Med., 2014, 371(22), 2083-2091.
[http://dx.doi.org/10.1056/NEJMoa1411099] [PMID: 25317743]
[21]
Kiiza, P.; Mullin, S.; Teo, K.; Adhikari, N.K.J.; Fowler, R.A. Treatment of Ebola-related critical illness. Intensive Care Med., 2020, 46(2), 285-297.
[http://dx.doi.org/10.1007/s00134-020-05949-z] [PMID: 32055888]
[22]
Goodman, J.L. Studying “secret serums”--toward safe, effective Ebola treatments. N. Engl. J. Med., 2014, 371(12), 1086-1089.
[http://dx.doi.org/10.1056/NEJMp1409817] [PMID: 25140857]
[23]
Beese, D.; Beckett, G. Ebola virus disease: Are you up to date? Pract. Nurs., 2019, 30(12), 572-577.
[http://dx.doi.org/10.12968/pnur.2019.30.12.572]
[24]
Nicastri, E.; Kobinger, G.; Vairo, F.; Montaldo, C.; Mboera, L.E.G.; Ansunama, R.; Zumla, A.; Ippolito, G. Ebola virus disease: Epidemiology, clinical features, management, and prevention. Infectious Disease Clinics, 2019, 33(4), 953-976.
[PMID: 31668200]
[25]
Frieden, T.R.; Damon, I.; Bell, B.P.; Kenyon, T.; Nichol, S. Ebola 2014--New challenges, new global response and responsibility. N. Engl. J. Med., 2014, 371(13), 1177-1180.
[http://dx.doi.org/10.1056/NEJMp1409903] [PMID: 25140858]
[26]
Chan, M. Ebola virus disease in West Africa--no early end to the outbreak. N. Engl. J. Med., 2014, 371(13), 1183-1185.
[http://dx.doi.org/10.1056/NEJMp1409859] [PMID: 25140856]
[27]
Appiah-Sakyi, K.; Mohan, M.; Konje, J.C. Ebola infection in pregnancy, an ongoing challenge for both the global health expert and the pregnant woman—A review. Eur. J. Obstet. Gynecol. Reprod. Biol., 2021, 258, 111-117.
[http://dx.doi.org/10.1016/j.ejogrb.2020.12.037] [PMID: 33421807]
[28]
Muzembo, B.A.; Ntontolo, N.P.; Ngatu, N.R.; Khatiwada, J.; Suzuki, T.; Wada, K.; Kitahara, K.; Ikeda, S.; Miyoshi, S.I. Misconceptions and rumors about Ebola virus Disease in Sub-Saharan Africa: A systematic review. Int. J. Environ. Res. Public Health, 2022, 19(8), 4714.
[http://dx.doi.org/10.3390/ijerph19084714] [PMID: 35457585]
[29]
Boddington, N.L.; Steinberger, S.; Pebody, R.G. Screening at ports of entry for Ebola virus Disease in England—A descriptive analysis of screening assessment data, 2014–2015. J. Public Health, 2022, 44(2), 370-377.
[http://dx.doi.org/10.1093/pubmed/fdaa216] [PMID: 33348353]
[30]
Gupta, V.; Jain, A.D.; Gill, N.S.; Gupta, K. Development and validation of HPLC method-A review. Int. Res. J. Pharm. Appl. Sci., 2012, 2(4), 17-25.
[31]
Malik, S.; Kishore, S.; Nag, S.; Dhasmana, A.; Preetam, S.; Mitra, O.; Figueroa, L.D.A.; Mohanty, A.; Chattu, V.K.; Assefi, M.; Padhi, B.K.; Sah, R. Ebola virus disease vaccines: Development, current perspectives & challenges. Vaccines, 2023, 11(2), 268.
[http://dx.doi.org/10.3390/vaccines11020268] [PMID: 36851146]
[32]
Saphire, E.O.; Schendel, S.L.; Gunn, B.M.; Milligan, J.C.; Alter, G. Antibody-mediated protection against Ebola virus. Nat. Immunol., 2018, 19(11), 1169-1178.
[http://dx.doi.org/10.1038/s41590-018-0233-9] [PMID: 30333617]
[33]
Pascal, K.E.; Dudgeon, D.; Trefry, J.C.; Anantpadma, M.; Sakurai, Y.; Murin, C.D.; Turner, H.L.; Fairhurst, J.; Torres, M.; Rafique, A. Development of clinical-stage human monoclonal antibodies that treat advanced Ebola virus disease in nonhuman primates. J. Infect. Dis., 2018, 218(S5), S612-S626.
[http://dx.doi.org/10.1093/infdis/jiy285]
[34]
Sivapalasingam, S.; Kamal, M.; Slim, R.; Hosain, R.; Shao, W.; Stoltz, R.; Yen, J.; Pologe, L.G.; Cao, Y.; Partridge, M.; Sumner, G.; Lipsich, L. Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: A randomised, first-in-human phase 1 study. Lancet Infect. Dis., 2018, 18(8), 884-893.
[http://dx.doi.org/10.1016/S1473-3099(18)30397-9] [PMID: 29929783]
[35]
Mulangu, S.; Dodd, L.E.; Davey, R.T., Jr; Mbaya, T.O.; Proschan, M.; Mukadi, D.; Manzo, L.M.; Nzolo, D.; Oloma, T.A.; Ibanda, A.; Ali, R.; Coulibaly, S.; Levine, A.C.; Grais, R.; Diaz, J.; Lane, H.C.; Tamfum, M.J.J.; Sivahera, B.; Camara, M.; Kojan, R.; Walker, R.; Kemp, D.B.; Cao, H.; Mukumbayi, P.; Kingebeni, M.P.; Ahuka, S.; Albert, S.; Bonnett, T.; Crozier, I.; Duvenhage, M.; Proffitt, C.; Teitelbaum, M.; Moench, T.; Aboulhab, J.; Barrett, K.; Cahill, K.; Cone, K.; Eckes, R.; Hensley, L.; Herpin, B.; Higgs, E.; Ledgerwood, J.; Pierson, J.; Smolskis, M.; Sow, Y.; Tierney, J.; Sivapalasingam, S.; Holman, W.; Gettinger, N.; Vallée, D.; Nordwall, J. A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med., 2019, 381(24), 2293-2303.
[http://dx.doi.org/10.1056/NEJMoa1910993] [PMID: 31774950]
[36]
Woolsey, C.; Geisbert, T.W. Current state of Ebola virus vaccines: A snapshot. PLoS Pathog., 2021, 17(12), e1010078.
[http://dx.doi.org/10.1371/journal.ppat.1010078] [PMID: 34882741]
[37]
Singh, S.; Kumar, N.K.; Dwiwedi, P.; Charan, J.; Kaur, R.; Sidhu, P.; Chugh, V.K. Monoclonal antibodies: A review. Curr. Clin. Pharmacol., 2018, 13(2), 85-99.
[http://dx.doi.org/10.2174/1574884712666170809124728] [PMID: 28799485]
[38]
Murin, C.D.; Gilchuk, P.; Crowe, J.E., Jr; Ward, A.B. Structural biology illuminates molecular determinants of broad ebolavirus neutralization by human antibodies for pan-ebolavirus therapeutic development. Front. Immunol., 2022, 12, 808047.
[http://dx.doi.org/10.3389/fimmu.2021.808047] [PMID: 35082794]
[39]
Brown, R.P. Reversed Phase High-Performance Liquid Chromatography: Theory, Practice and Biochemical Applications; Wiley, 1982.
[40]
Nikolin, B.; Imamović, B.; Vuk, M.S.; Sober, M. High performance liquid chromatography in pharmaceutical analyses. Bosn. J. Basic Med. Sci., 2004, 4(2), 5-9.
[http://dx.doi.org/10.17305/bjbms.2004.3405] [PMID: 15629016]
[41]
Sethi, P.D. High-Performance Liquid Chromatography, Quantitative Analysis of Pharmaceutical Formulations; CBS Publishers and Distributors: New Delhi, 2001, pp. 116-120.
[42]
Kamble, S.; Agrawal, S.; Pagade, S.; Patil, R.; Chaugule, N.; Patil, A. A review on high performance liquid chromatography (HPLC). Asian J. Pharm. Anal., 2023, 13(1), 61-65.
[http://dx.doi.org/10.52711/2231-5675.2023.00011]
[43]
Perry, G.A.; Jackson, J.D.; McDonald, T.L.; Crouse, D.A.; Sharp, J.G. Purification of monoclonal antibodies using high performance liquid chromatography (HPLC). Prep. Biochem., 1984-1985, 14(5), 431-447.
[http://dx.doi.org/10.1080/00327488408061779] [PMID: 6336002]
[44]
Meher, U.; Syed, I.P. Development and validation of stability indicating RP-HPLC method to separate low levels of Atoltivimab, Maftivimab, and Odesivimab and other related compounds. Eur. J. Biomed. Pharm. Sci, 2022, 9(9), 77-82.
[45]
Deschamps, J.R.; Hildreth, J.E.K.; Derr, D.; August, J.T. A high-performance liquid chromatographic procedure for the purification of mouse monoclonal antibodies. Anal. Biochem., 1985, 147(2), 451-454.
[http://dx.doi.org/10.1016/0003-2697(85)90296-9] [PMID: 4014689]
[46]
Burchiel, S.W.; Billman, J.R.; Alber, T.R. Rapid and efficient purification of mouse monoclonal antibodies from ascites fluid using high performance liquid chromatography. J. Immunol. Methods, 1984, 69(1), 33-42.
[http://dx.doi.org/10.1016/0022-1759(84)90274-6] [PMID: 6715888]
[47]
Swartz, M.E.; Krull, I. Method validation and robustness. LC GC N. Am., 2006, 24(5), 480-490.
[48]
González, G.A.; Herrador, A.M. A practical guide to analytical method validation, including measurement uncertainty and accuracy profiles. Trends Analyt. Chem., 2007, 26(3), 227-238.
[http://dx.doi.org/10.1016/j.trac.2007.01.009]
[49]
Ambrogelly; Liu, Y.H.; Li, H.; Mengisen; Yao; Xu, W.; Carlson, C.S. Characterization of antibody variants during process development: The tale of incomplete processing of N-terminal secretion peptide. MAbs, 2012, 4(6), 701-709.
[http://dx.doi.org/10.4161/mabs.21614] [PMID: 22932441]
[50]
Navas, N.; Herrera, A.; Ortega, M.A.; García, S.A.; Cabeza, J.; Rodríguez, C.L. Quantification of an intact monoclonal antibody, rituximab, by (RP)HPLC/DAD in compliance with ICH guidelines. Anal. Bioanal. Chem., 2013, 405(29), 9351-9363.
[http://dx.doi.org/10.1007/s00216-013-7368-1] [PMID: 24121431]
[51]
Matsuda, Y.; Leung, M.; Tawfiq, Z.; Fujii, T.; Mendelsohn, B.A. In-situ reverse phased HPLC analysis of intact antibody-drug conjugates. Anal. Sci., 2021, 37(8), 1171-1176.
[http://dx.doi.org/10.2116/analsci.20P424] [PMID: 33518587]
[52]
Fekete, S.; Dong, M.W.; Zhang, T.; Guillarme, D. High resolution reversed phase analysis of recombinant monoclonal antibodies by ultra-high pressure liquid chromatography column coupling. J. Pharm. Biomed. Anal., 2013, 83, 273-278.
[http://dx.doi.org/10.1016/j.jpba.2013.05.022] [PMID: 23770782]
[53]
Fekete, S.; Gassner, A.L.; Rudaz, S.; Schappler, J.; Guillarme, D. Analytical strategies for the characterization of therapeutic monoclonal antibodies. Trends Analyt. Chem., 2013, 42, 74-83.
[http://dx.doi.org/10.1016/j.trac.2012.09.012]
[54]
Fekete, S.; Guillarme, D. Reversed-phase liquid chromatography for the analysis of therapeutic proteins and recombinant monoclonal antibodies. LC GC Eur., 2012, 25, 540-550.
[55]
Fekete, S.; Beck, A.; Fekete, J.; Guillarme, D. Method development for the separation of monoclonal antibody charge variants in cation exchange chromatography, Part II: pH gradient approach. J. Pharm. Biomed. Anal., 2015, 102, 282-289.
[http://dx.doi.org/10.1016/j.jpba.2014.09.032] [PMID: 25459925]
[56]
Snyder, L.R. Gradient elution. In: HPLC: Advances and Per-spectives; Horvath, C., Ed.; Academic Press: New York, 1980; Vol. 1, pp. 208-316.
[57]
Snyder, L.R.; Kirkland, J.J.; Glajch, J.L. Practical HPLC Method Development, 2nd ed; John Wiley & Sons Inc.: New York, 1997.
[http://dx.doi.org/10.1002/9781118592014]
[58]
Lundell, N.; Schreitmüller, T. Sample preparation for peptide mapping--A pharmaceutical quality-control perspective. Anal. Biochem., 1999, 266(1), 31-47.
[http://dx.doi.org/10.1006/abio.1998.2919] [PMID: 9887211]
[59]
Krull, I.S.; Rathore, A. Current application of UHPLC in biotechnology. Part: 1. LC GC N. Am., 2011, 29, 838-852.
[60]
Fekete, S.; Veuthey, J.L.; Eeltink, S.; Guillarme, D. Comparative study of recent wide-pore materials of different stationary phase morphology, applied for the reversed-phase analysis of recombinant monoclonal antibodies. Anal. Bioanal. Chem., 2013, 405(10), 3137-3151.
[http://dx.doi.org/10.1007/s00216-013-6759-7] [PMID: 23358675]
[61]
Todoroki, K. Development of HPLC analysis methods for therapeutic monoclonal antibodies. Yakugaku Zasshi, 2015, 135(2), 213-218.
[http://dx.doi.org/10.1248/yakushi.14-00213-4] [PMID: 25747215]
[62]
Bhatt, M.; Alok, A.; Kulkarni, B.B. Method development and qualification of pH-based CEX UPLC method for monoclonal antibodies. BioTech, 2022, 11(2), 19.
[http://dx.doi.org/10.3390/biotech11020019] [PMID: 35822792]
[63]
Singh, S.K.; Lee, K.H. Characterization of monoclonal antibody glycan heterogeneity using hydrophilic interaction liquid chromatography-mass spectrometry. Front. Bioeng. Biotechnol., 2022, 9, 805788.
[http://dx.doi.org/10.3389/fbioe.2021.805788] [PMID: 35087805]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy