title: LC-MS/MS multiplexed assay for the quantitation of a therapeutic protein BMS-986089 and the target protein Myostatin.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: D'Arienzo
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lou
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kozhich
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Malavi
authors.initials: M
authors.lastname: Madireddi
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Anjaneya
authors.initials: A
authors.lastname: Chimalakonda
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tymiak
authors.affiliation: Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, USA.
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Olah
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid / Q000191:economics / Q000379:methods*; D003362:Cost-Benefit Analysis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055435:Myostatin / Q000032:analysis* / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D014357:Trypsin / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D055435:Myostatin; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014357:Trypsin
keywords: LC–MS/MS-based multiplexed detection; surrogate peptides; target protein; therapeutic protein