Zhao Yue, Liu Guowen, Kwok Suk, Jones Barry R, Liu Jane, Marchisin David, Joyce Philip E, Peterson Jon, Shen Jim X
Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Co., Route 206 & Province Line Road, Princeton, NJ 08543, USA.
DMPK-Clinical Bioanalytical, Agios Pharmaceuticals, Cambridge, MA 02139, USA.
Bioanalysis. 2018 Jan;10(1):23-33. doi: 10.4155/bio-2017-0208. Epub 2017 Dec 14.
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.
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.
重组FGF21类似物作为2型糖尿病以及其他代谢紊乱的潜在治疗药物正在受到广泛研究。内源性FGF21常被用作替代药效学（PD）生物标志物来评估药物疗效和安全性。结果与方法：使用针对天然FGF21特定结构域产生的单克隆抗体作为捕获试剂进行免疫捕获。免疫捕获后，进行酶解，并通过选择性反应监测利用液相色谱-串联质谱法监测一种天然FGF21特异性胰蛋白酶肽段。
我们成功开发并验证了一种生物分析方法，该方法具有特异性，可将内源性FGF21与序列与内源性分子几乎相同的重组治疗药物区分开来。
