Challenges with development of a pharmacokinetics assay to measure a variably glycosylated fusion protein
| Autor: | Jeff Lutman, Saloumeh K Fischer, Sid Sukumaran, Catherine Huang, Tracy Bentley, Keyang Xu, Gizette Sperinde, Luna Liu, Martha Hokom, Kathi Williams |
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| Rok vydání: | 2021 |
| Předmět: |
Bioanalysis
Glycosylation Clinical Biochemistry Measure (physics) Enzyme-Linked Immunosorbent Assay General Medicine Fusion protein N-Acetylneuraminic Acid Analytical Chemistry Sialic acid law.invention Medical Laboratory Technology chemistry.chemical_compound Pharmacokinetics chemistry Biochemistry law Recombinant DNA Humans General Pharmacology Toxicology and Pharmaceutics |
| Zdroj: | Bioanalysis. 14(1) |
| ISSN: | 1757-6199 |
| Popis: | Aim: Development of recombinant fusion proteins as drugs poses unique challenges for bioanalysis. This paper describes a case study of a glycosylated fusion protein, where variable glycosylation, matrix interference and high sensitivity needs posed unique challenges. Results: Six different assay configurations, across four different platforms were evaluated for measurement of drug concentrations. Two platforms that achieved the assay requirements were Simoa HD-1 and immune-capture LC–MS/MS-based assay. Conclusion: Both, Simoa HD-1 and the mass spectrometry-based methods were able to detect total drug by providing the adequate matrix tolerance, required sensitivity and detection of all the various glycosylated fusion proteins to support clinical sample analysis. The mass spectrometry-based method was selected due to robustness and ease of method transfer. |
| Databáze: | OpenAIRE |
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