Background and importance Adalimumab (Humira 100 mg/mL) is a monoclonal antibody (mAb) which is used for the treatment of psoriasis, rheumatoid arthritis and Crohn’s disease in adults and children. Humira is injected under the skin. The dose for a child is calculated according to the child’s weight and the medicine is supplied in prefilled syringes that are self-administered at home. Adalimumab has low stability after the vial is open and therefore it is necessary to study its stability under the usual conditions which the prefilled syringes will be exposed. In this context, the charge variant characterisation allows for the detection of structural changes in the drug.
Aim and objectives The objective of the study was to characterise the charge variants of adalimumab under stress conditions (ie, high temperature (60°) and smooth shaking) by liquid chromatography coupled to UV and mass spectrometry detection in order to assess the impact of mishandling adalimumab in prefilled syringes.
Material and methods Prefilled syringes were prepared with different volumes of Humira (100 mg/mL) and placed at 60°C for 3 hours (to ensure there was degradation of adalimumab and also validation of the method) or underwent smooth shaking at room temperature for 1 hour. An UHPLC-HESI/MS (Orbitrap) was the platform used for the analysis. The column used for the separation was a MabPac SCX-10 RS 2.1 mm×5 mm column, 5µm (Thermo Fisher Scientific).
Results Several charge variants were characterised for adalimumab (basic and acid variants). Significant differences were detected in this charge variant profile after samples were subjected to 60°C. The charge variants of adalimumab after sample smooth shaking remained unchanged.
Conclusion and relevance Exposure of adalimumab to 60°C modified the chemical structure. The increase in positive charges in the primary structure indicated the increase in basic variants. Therefore, it is highly recommended to keep prefilled syringes refrigerated during transport and storage. On the other hand, agitation of adalimumab solution did not affect the charge variant profiles and thus no particular recommendation is needed.
References and/or acknowledgements Funded by Project FIS: PI-17/00547 (Instituto Carlos III, Ministerio de Economía y Competitividad, Spain), which means that it was also partially supported by the European Regional Development Funds.
No conflict of interest.
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