Detection of the Human Anti-ActRII Antibody Bimagrumab in Serum by Means of Affinity Purification, Tryptic Digestion, and LC-HRMS

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PURPOSE: Inhibitors of the ActRII signaling pathways represent promising therapeutics for the treatment of muscular diseases, but also pose risks as performance-enhancing agents in sports. Bimagrumab is a human anti-ActRII antibody which was found to increase muscle mass and function by blocking ActRII signaling. As it has considerable potential for being misused as doping agent in sports, the aim of this study was to develop a mass spectrometric detection assay for doping control serum samples.

EXPERIMENTAL DESIGN: Within this study, a detection method for Bimagrumab in human serum was developed, which combines ammonium sulfate precipitation and affinity purification with proteolytic digestion and LC-HRMS. To facilitate the unambiguous identification of the diagnostic peptides, an orthogonal IM separation was additionally performed.

RESULTS: The assay was successfully validated and the analysis of clinical samples demonstrated its fitness for purpose for an application in routine doping control analysis.

CONCLUSIONS AND CLINICAL RELEVANCE: Although no myostatin inhibitors have obtained clinical approval yet, the proactive development of detection methods for emerging doping agents represents a key aspect of preventive doping research. The presented approach will expand the range of available tests for novel protein therapeutics and can readily be modified to include further target analytes.

OriginalspracheEnglisch
Aufsatznummer1700120
ZeitschriftProteomics. Clinical applications
Jahrgang12
Heft3
Seitenumfang11
ISSN1862-8346
DOIs
PublikationsstatusVeröffentlicht - 11.12.2017

ID: 3287439

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