Highly selective and sensitive measurement of active forms of FGF21 using novel immunocapture enrichment with LC–MS/MS

Autor: Jim X Shen, Yue Zhao, Jon E. Peterson, Philip Joyce, Barry R Jones, Guowen Liu, Jane Liu, David Marchisin, Suk Kwok
Rok vydání: 2018
Předmět:
Zdroj: Bioanalysis. 10:23-33
ISSN: 1757-6199
1757-6180
DOI: 10.4155/bio-2017-0208
Popis: Aim: Recombinant FGF21 analogs are under wide ranging investigations as a potential therapeutic agent for Type 2 diabetes, as well as other metabolic disorders. The endogenous FGF21 is often used as a surrogate pharmacodynamic(PD) biomarker to assess drug efficacy and safety. Results & methodology: Immunocapture was performed using a monoclonal antibody which had been generated to bind to specific domain of native FGF21 as the capture reagent. After immunocapture, enzymatic digestion was performed and a native FGF21-specific tryptic peptide was monitored using LC–MS/MS by selective reaction monitoring. Conclusion: We have successfully developed and validated a bioanalytical assay which provides the specificity to differentiate the endogenous FGF21 from the recombinant therapeutic agent which has nearly identical sequence to the endogenous molecule.
Databáze: OpenAIRE