5PSQ-138 Impact of high temperature, shaking and light on quality of the therapeutic peptide teduglutide (Revestive) evaluated by LC/MS/MS (Orbitrap) peptide mapping analysis and stress

• Published in: European journal of hospital pharmacy. Science and practice 2022-03, Vol.29 (Suppl 1), p.A161-A162
• Main Authors: Pérez-Robles, R, Navas, N, Clemente-Bautista, S, Jiménez-Lozano, I, Cabañas-Poy, MJ, Cabeza, J, Salmerón-García, A
• Format: Article
• Language: English
• Subjects: Conflicts of interest; Light; Peptides; Section 5: Patient safety and quality assurance
• ISSN: 2047-9956; 2047-9964
• DOI: 10.1136/ejhpharm-2022-eahp.339

Background and importance Teduglutide (Revestive) is a recombinant human GLP-2 analogue indicated in the treatment of short bowel syndrome, a serious and highly disabling condition which results from either loss of portions of intestine or loss of critical intestinal function. A proteinaceous-based medicine, teduglutide is indicated to have low stability, thus the study of the effect of possible in- use mishandling and in- stress conditions are welcome to gain knowledge of its stability and degradation. Aim and objectives To evaluate the impact on teduglutide’s chemical structure when subjected to in-use mishandling and when it is degraded by the characterisation of its post-translational modifications (PTMs) obtained by liquid chromatography with tandem mass spectrometry (LC/MS/MS) (Orbitrap) peptide mapping analysis after submitting teduglutide samples to 40°C and 60 °C, to smooth shaking and to accelerated light exposition. Material and methodsSamples of reconstituted teduglutide (Revestive) were submitted to 40°C and 60°C (3 hours), to smooth shaking (3 hours) and to accelerated light exposition (24 hours). Tryptic digestion was performed on these samples and the resulted fragments were separated and quantified by LC/MS/MS. BiopharmaFinder 3.1 software (Thermo Scientific) was used for PTMs identification.ResultsDifferent PTMs related to the quality of the medicine were monitored in the primary structure of teduglutide (ie, deamidations, isomerisations and oxidations) [1]. No changes in the PTMs profiles were found in samples subjected to temperature and agitation in comparison to the PTMs profiles of fresh teduglutide. High percentages of oxidations were detected in the samples submitted to light exposition.Conclusion and relevanceThe exposition to light modified the PTMs profile of teduglutide inducing oxidations in the primary structure (methionine and tryptophan residues). These might affect teduglutide’s security, efficacy and quality. Therefore, it is highly recommended to protect the drug from light during in-use manipulation. For temperature exposition (40°C and 60°C) and agitation, the PTMs profile was not modified, thus no specific recommendations need be noted in this regard.References and/or acknowledgements 1. Hmiel LK, et al. Anal Bioanal Chem 2015;407:79–94. Raquel Pérez-Robles is currently granted a postdoctoral position from the Junta de Andalucía, Spain.Conflict of interestNo conflict of interest