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Research Article

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

    Yue Zhao

    *Author for correspondence:

    E-mail Address: yue.zhao@bms.com

    Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA

    ,
    Guowen Liu

    DMPK-Clinical Bioanalytical, Agios Pharmaceuticals, Cambridge, MA 02139, USA

    ,
    Suk Kwok

    Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA

    ,
    Barry R Jones

    Q2 Solutions, 19 Brown Rd, Ithaca, NY 14850, USA

    ,
    Jane Liu

    Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA

    ,
    David Marchisin

    Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA

    ,
    Philip E Joyce

    Q2 Solutions, 19 Brown Rd, Ithaca, NY 14850, USA

    ,
    Jon Peterson

    Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA

    &
    Jim X Shen

    *Author for correspondence:

    E-mail Address: yue.zhao@bms.com

    Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA

    Published Online:https://doi.org/10.4155/bio-2017-0208

    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.

    Papers of special note have been highlighted as: • of interest

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