Application of capillary electrophoresis in stability studies of some biopharmaceutical products.

Abstract

Since inherent physicochemical complexity of biopharmaceuticals makes them susceptible to the chemical and physical instability, one of the crucial parts of their quality control is stability studies. It is obvious that, without reliable analytical tools with a stability indicating capacity, stability studies are not possible. Capillary electrophoresis (CE) is a poweful analytical technique and along with the extreme advancements in biopharmaceutical industry over the past two decades, considerable effort has been dedicated toward developing CE-based methods applicable for the characterization and quality control of biopharmaceuticals. Considering the importance of stability studies in the quality control of biopharmaceuticals and the important role of capillary electro-migration methods in their quality control, the main objective of this thesis is application of CE in the stability studies of some biopharmaceutical products. To investigate the usefulness of CE technique in the stability studies of biopharmaceuticals, heparin as a complex carbohydrate, buserelin as a linear peptide and octreotide as a cyclic peptide have been selected as candidate biopharmaceuticals. Then, some novel stability indicating CE-based methods have been developed and validated for the quantitative analysis of candidate biopharmaceutical products, in both the pharmaceutical formulations and force degraded samples. Afterward, the developed methods have been successfully employed for the evaluation of the degradation behaviors of examined biopharmaceuticals under stress conditions and estimation of the involved kinetics in their degradation. Moreover, the application of CE in combination with ion trap mass spectrometry (IT-MS) has been explored for the reliable analysis of octreotide, identification of its major degaradtion products and investigation of the degradation pathways responsible for their formation under stress conditions. In addition, a review about the applications of electro-migration methods in the quality control of biopharmaceuticals and a summarized review about the stability studies of biopharmaceuticals under stress conditions have been prepared. By taking the findings of the present thesis into the consideration, it can be concluded that, CE-based methods could be successfully applied as reliable tools in quality control laboratories to assess the quality and stability of biopharmaceuticals in bulk and finished products. In addition CE-based methods particularly in combination with mass detector could play an important role in the preparation of the stability profiles of biopharmaceuticals through the investigation of the kinetics could govern their degradation, characterization of the pathways could involve in their degradation and identification of their possible degradation products.