title: The Effects of Light-Accelerated Degradation on the Aggregation of Marketed Therapeutic Monoclonal Antibodies Evaluated by Size-Exclusion Chromatography With Diode Array Detection.
abstract: Research into the effects that exposure to light can have on therapeutic proteins is essential for ensuring the quality and safety of the medicines in which they are used. It is important to understand the effects of light on aggregation to help avoid undesirable colloidal instabilities, both in the original medicines and in the formats in which they are finally administered. In this study, 5 marketed therapeutic mAbs, namely bevacizumab, cetuximab, infliximab, rituximab, and trastuzumab, were investigated for this purpose. The medicines and 2 diluted preparations in 0.9 NaCl (2 mg/mL and 5 mg/mL)-commonly used in clinical practice-were subjected to controlled light-accelerated degradation. The formation of aggregates was monitored by size-exclusion chromatography. The results indicated that light induced protein aggregation. This process of protein damage was influenced above all by mAb concentration, although the particular characteristics of each mAb were also important. Photodegradation also produced the fragmentation of the mAbs. The damage caused to the mAbs as a result of light-induced aggregation and/or fragmentation was demonstrated both in the medicines and in the diluted preparation forms. These findings should be carefully considered when handling the medicines for administration and when recommending beyond-use dates in normal hospital conditions.
authors.affiliation: Department of Analytical Chemistry, Faculty of Science, University of Granada, E-18071 Granada, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Hernández-Jiménez
authors.affiliation: UGC Intercentro Interniveles Farmacia Granada, "San Cecilio Hospital," Biomedical Research Institute ibs.GRANADA, Hospitales Universitarios de Granada, E-18012 Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salmerón-García
authors.affiliation: UGC Intercentro Interniveles Farmacia Granada, "San Cecilio Hospital," Biomedical Research Institute ibs.GRANADA, Hospitales Universitarios de Granada, E-18012 Granada, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Cabeza
authors.affiliation: Department of Embryology and Human Anatomy, Medicine Faculty, University of Granada, E-18012 Granada, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Vélez
authors.affiliation: Department of Analytical Chemistry, Faculty of Science, University of Granada, E-18071 Granada, Spain.
authors.forename: Luis Fermín
authors.initials: LF
authors.lastname: Capitán-Vallvey
authors.affiliation: Department of Analytical Chemistry, Science Faculty, Biomedical Research Institute ibs.GRANADA, University of Granada, E-18071 Granada, Spain. Electronic address: natalia@ugr.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Navas
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002850:Chromatography, Gel; D006801:Humans; D008027:Light; D066329:Protein Aggregates / Q000528:radiation effects*; D059748:Proteolysis / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D066329:Protein Aggregates
keywords: biopharmaceutics: bevacizumab, cetuximab, infliximab, rituximab, trastuzumab; light stress; monoclonal antibody aggregation; size-exclusion chromatography