Quantitation of certolizumab pegol by validated liquid chromatography methods

Authors

  • Clóvis Dervil Appratto Cardoso Júnior Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
  • Bruna Xavier Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
  • Rafaela Ferreira Perobelli Dumoncel Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
  • Francielle Santos da Silva Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
  • Sérgio Luiz Dalmora Universidade Federal de Santa Maria, Santa Maria, RS, Brazil https://orcid.org/0000-0003-0103-4416

DOI:

https://doi.org/10.1590/

Keywords:

Certolizumab pegol, Monoclonal antibody, Size exclusion liquid chromatography, Reversed-phase liquid chromatography, Validation

Abstract

Certolizumab pegol (CZP) is a Fab’ fragment of the humanized antibody with anti-TNF-α activity that is indicated as therapy for Crohn’s disease and rheumatoid arthritis. Using a BioSep-SEC-S3000 column (300 x 4.6 mm i.d., 5 µm particle size), a size exclusion liquid chromatography (SEC) method was developed. Mobile phase A consisted of 100 mM monobasic sodium phosphate and 200 mM sodium chloride (pH 7.0), while mobile phase B was ethanol (95:5, v/v), and the analysis was performed using a diode array detector (DAD) set to 214 nm and a flow rate of 0.5 ml min-1. In addition, a reversed-phase liquid chromatography (RP-LC) method based on gradient elution was developed on a Zorbax 300 SB C18 column (150 mm x 4.6 mm i.d., 3.5 µm particle size) kept at 80 °C. Mobile phase A was 0.1% (v/v) TFA in ultrapure water, and mobile phase B was a mixture of propanol, acetonitrile, ultrapure water and TFA (70 + 20 + 9.9 + 0.1, v/v) operated at a flow rate of 1.0 ml min-1, and DAD was applied at 214 nm. CZP elution was achieved with retention times of 5.6 min and 9.0 min for SEC and RP-LC, respectively.

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References

Agência Nacional de Vigilância Sanitária (Brasil). Resolução nº 166, de 24 de julho de 2017. Dispõe sobre a validação de métodos analíticos e dá outras providências[Internet]. Brasília (DF): Ministério da Saúde, 2017. 21 p. Available from: http://antigo.anvisa.gov.br/documents/10181/2721567/RDC_166_2017_COMP.pdf/d5f b92b3-6c6b-4130-8670- 4e3263763401

» http://antigo.anvisa.gov.br/documents/10181/2721567/RDC_166_2017_COMP.pdf/d5f b92b3-6c6b-4130-8670- 4e3263763401

Deeks, ED. Certolizumab pegol: a review in inflammatory autoimmune diseases. BioDrugs. 2016;30(6):607-617.

EMA. Cimzia, INN-Certolizumab pegol. Product Information. European Medicines Agency. 2014. Available from: https:// www.ema.europa.eu/en/documents/product-information/cimzia-epar-product-information_en.pdf

» https:// www.ema.europa.eu/en/documents/product-information/cimzia-epar-product-information_en.pdf

Fekete S, Veuthey J, Guillarme D. Achievable separation performance andanalysistime incurrentliquidchromatographic practice for monoclonal antibody separations. J Pharm Biomed Anal. 2017;141:59-69.

Goyon A, Beck A, Colas O, Sandra K, Guillarme D, Fekete S. Evaluation of size exclusion chromatography columns packed with sub-3 μm particles for the analysis of biopharmaceutical proteins. J Chromatogr A. 2017;1498:80-89.

Hernández-Jiménez J, Martínez-Ortega A, Salmerón- García A, Cabeza J, Prados JC, Ortíz R, Navas N. Study of aggregation in therapeutic monoclonal antibodies subjected to stress and long-term stability tests by analyzing size exclusion liquid chromatographic profiles. Int J Biol Macromol. 2018;118:511-524.

Horton S, Walsh C, Emery P. Certolizumab pegol for the treatment of rheumatoid arthritis. Expert Opin Biol Ther. 2012;12(2):235-249.

ICH. Validation of Analytical Procedures: Text and MethodologyQ2(R1).International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). 2005. Available from: https://database.ich.org/ sites/default/files/Q2%28R1%29%20Guideline.pdf

» https://database.ich.org/ sites/default/files/Q2%28R1%29%20Guideline.pdf

Launois R, Avouac B, Berenbaum F, Blin O, Bru I, Fautrel B, et al. Comparison of Certolizumab Pegol with Other Anticytokine Agents for Treatment of Rheumatoid Arthritis: A Multiple-treatment Bayesian Metaanalysis. J Rheumatol. 2011;38(5):835-845.

Lenth RV. Quick and easy analysis of unreplicated factorials. Technometrics. 1989;31(4):469-473.

Martínez-Ortega A, Herrera A, Salmerón-García A, Cabeza J, Cuadros-Rodríguez L, Navas N. Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab. J Pharm Anal. 2016;6(2):117-124.

Mitoma H, Horiuchi T, Tsukamoto H, Ueda N. Molecular mechanisms of action of anti-TNF-α agents-Comparison among therapeutic TNF-α antagonists. Cytokine. 2016;101:56-63.

Navas N, Herrera A, Martínez-Ortega A, Salmerón-García A, Cabeza J, Cuadros-Rodríguez 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.

Paul M, Vieillard V, Jaccoulet E, Astier A. Long-term stability of diluted solutions of the monoclonal antibody rituximab. Int J Pharm. 2012;436:282-290.

Perobelli RF, Xavier B, da Silveira AR, Remuzzi GL, Motta LGJ, Dalmora SL. Quantitation of the monoclonal antibody Denosumab by bioassay and validated LC methods. Int J Biol Macromol. 2018;119:96-104.

Ratto JJ, O’Conner SR, Distler AR, Wu G, Hummel D, Treuheit MJ, et al. Ethanol-sodium chloride-phosphate mobile phase for size-exclusion chromatography of poly (ethylene glycol) modified proteins. J Chromatogr A. 1997;763:337-344.

Shabir GA, Lough WJ, Arain SA, Bradshaw TK. Evaluation and Application of Best Practice in Analytical Method Validation. J Liq Chromatogr Relat Technol. 2007;30(3):311-333.

Shahbazi M, Zahedy ET, Kiumarsi S, Soltanabad MH, Azar SS, Amini H. Determination of pegfilgrastim aggregates by size-exclusion high-performance liquid chromatography on a methacrylate-based column. Biologicals. 2017;46:153-158.

Shepard HM, Phillips GL, Thanos CD, Feldmann M. Developments in therapy with monoclonal antibodies and related proteins. Clin Med (Lond). 2017;17(3):220-232.

Stamm FP, Calegari GZ, de Freitas GW, Souto RB, Porto LP, Cardoso Jr. CDA, Dalmora SL. Assessment of recombinant human parathyroid hormone: correlation of LC methods with bioassays. Analyst. 2013;138:1419-1426.

Ueda T. Next-generation optimized biotherapeutics-A review and preclinical study. Biochim Biophys Acta Proteins Proteom. 2014;1844(11):2053-2057.

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Published

2023-11-03

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How to Cite

Quantitation of certolizumab pegol by validated liquid chromatography methods. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e23020. https://doi.org/10.1590/