LC-MS/MS multiplexed assay for the quantitation of a therapeutic protein BMS-986089 and the target protein Myostatin

Bioanalysis
Yongxin ZhuTimothy V Olah

Abstract

Therapeutic protein discovery study highlights the need for the development of quantitative bioanalytical methods for determining the levels of both the therapeutic protein and the target protein, as well. For the quantitation of BMS-986089, both accuracy (99-103%) and precision (2.4-12%) were obtained for the analysis of the surrogate peptide (ITYGGNSPVQEFTVPGR), in addition to the accuracy (100-108%) and precision (0.7-18%) that were obtained for the analysis of the surrogate peptide (VVSVLTVLHQDWLNGK). For Myostatin, accuracy (94-103%) and precision (2.4-14.9%) were obtained for the analysis of the surrogate peptide (IPAMVVDR). The developed method was applied to the analysis of samples following dosing of BMS-986089 to mice. This method highlights the potential of LC-MS/MS-based methods to eventually assess in vivo drug-target engagement.

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Citations

Feb 6, 2018·Scientific Reports·M Pirruccello-StraubA Donovan
Feb 14, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andreas LodbergMarco Eijken
Sep 11, 2020·Journal of Bone Metabolism·Joonho Suh, Yun-Sil Lee
Jan 27, 2021·Scientific Reports·Hiroyasu MuramatsuJunichi Nezu
May 4, 2021·The Journal of Clinical Investigation·Se-Jin Lee
Oct 30, 2018·Analytical Chemistry·Hiroshi SugimotoMark G Qian
Sep 15, 2021·Endocrine Reviews·Buel D Rodgers, Christopher W Ward

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Methods Mentioned

BETA
protein assay

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