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

  • Bioanalysis. 2016 Feb;8(3):193-204. doi: 10.4155/bio.15.238.
Yongxin Zhu  1 ,  Celia D'Arienzo  1 ,  Zhen Lou  1 ,  Alexander Kozhich  1 ,  Malavi Madireddi  1 ,  Anjaneya Chimalakonda  1 ,  Adrienne Tymiak  1 ,  Timothy V Olah  1
Affiliations
  • 1. Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
PMID: 26811930 DOI: 10.4155/bio.15.238
Abstract

Background: 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.

Results: 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).

Conclusion: 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.

Keywords
LC–MS/MS-based multiplexed detection; surrogate peptides; target protein; therapeutic protein.
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