Design of a strong cation exchange methodology for the evaluation of charge heterogeneity in glatiramer acetate
| Autor: | Carlos E. Espinosa-de la Garza, Luis F. Flores-Ortiz, Víctor R. Campos-García, Emilio Medina-Rivero, Jesús Padilla-Calderón, Carlos A. López-Morales, Eleuterio Benites-Zaragoza, Armando Jiménez-Miranda, Daniel Herrera-Fernández, Néstor O. Pérez |
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| Rok vydání: | 2017 |
| Předmět: |
Quality Control
0301 basic medicine Clinical Biochemistry Margin of error Pharmaceutical Science Sensitivity and Specificity 01 natural sciences Analytical Chemistry 03 medical and health sciences Adenosine Triphosphate Cations Drug Discovery medicine Critical to quality Sensitivity (control systems) Glatiramer acetate Spectroscopy Probability Chromatography Chemistry 010401 analytical chemistry Reproducibility of Results Charge (physics) Glatiramer Acetate Reference Standards Chromatography Ion Exchange 0104 chemical sciences 030104 developmental biology Peptides Biological system Retention time medicine.drug |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 132:133-140 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2016.10.002 |
| Popis: | Complex pharmaceuticals are in demand of competent analytical methods able to analyze charge heterogeneity as a critical quality attribute (CQA), in compliance with current regulatory expectations. A notorious example is glatiramer acetate (GA), a complex polypeptide mixture useful for the treatment of relapsing-remitting multiple sclerosis. This pharmaceutical challenges the current state of analytical technology in terms of the capacity to study their constituent species. Thus, a strong cation exchange methodology was designed under the lifecycle approach to support the establishment of GA identity, trough the evaluation of its chromatographic profile, which acts as a charge heterogeneity fingerprint. In this regard, a maximum relative margin of error of 5% for relative retention time and symmetry factor were proposed for the analytical target profile. The methodology met the proposed requirements after precision and specificity tests results, the former comprised of sensitivity and selectivity. Subsequently, method validation was conducted and showed that the method is able to differentiate between intact GA and heterogeneity profiles coming from stressed, fractioned or process-modified samples. In summary, these results provide evidence that the method is adequate to assess charge heterogeneity as a CQA of this complex pharmaceutical. |
| Databáze: | OpenAIRE |
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