title: Design of a strong cation exchange methodology for the evaluation of charge heterogeneity in glatiramer acetate.
abstract: 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.
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Víctor R
authors.initials: VR
authors.lastname: Campos-García
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: López-Morales
authors.affiliation: Unidad de Calidad, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Benites-Zaragoza
authors.affiliation: Unidad de Calidad, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Jiménez-Miranda
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Espinosa-de la Garza
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Herrera-Fernández
authors.affiliation: Unidad de Calidad, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: Padilla-Calderón
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico.
authors.forename: Néstor O
authors.initials: NO
authors.lastname: Pérez
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico. Electronic address: luis.flores@probiomed.com.mx.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Flores-Ortiz
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán s/n, Tenancingo, Mexico. Electronic address: emilio.medina@probiomed.com.mx.
authors.forename: E
authors.initials: E
authors.lastname: Medina-Rivero
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D002412:Cations; D002852:Chromatography, Ion Exchange / Q000379:methods*; D000068717:Glatiramer Acetate / Q000032:analysis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011336:Probability; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002412:Cations; D010455:Peptides; D000068717:Glatiramer Acetate; D000255:Adenosine Triphosphate
keywords: ATP; Glatiramer acetate; SCX-UPLC; UPLC method; Validation