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 |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Bioanalysis medicine.drug_class Clinical Biochemistry Endogeny Monoclonal antibody Tandem mass spectrometry Analytical Chemistry law.invention 03 medical and health sciences Tandem Mass Spectrometry Liquid chromatography–mass spectrometry law Lc ms ms medicine Humans General Pharmacology Toxicology and Pharmaceutics Chemistry General Medicine Biomarker (cell) Fibroblast Growth Factors Medical Laboratory Technology 030104 developmental biology Biochemistry Recombinant DNA Chromatography Liquid |
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 |
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