Yue Zhao1, Guowen Liu2, Suk Kwok1, Barry R Jones3, Jane Liu1, David Marchisin1, Philip E Joyce3, Jon Peterson1, Jim X Shen1. 1. Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA. 2. DMPK-Clinical Bioanalytical, Agios Pharmaceuticals, Cambridge, MA 02139, USA. 3. Q2 Solutions, 19 Brown Rd, Ithaca, NY 14850, USA.
Abstract
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.
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.