Therapeutic proteins are a continuously growing class of pharmaceuticals and 
comprise several drug candidates with potential performance-enhancing 
properties. In particular, activin receptor competitors, such as the ActRII-Fc 
fusion proteins Sotatercept (ActRIIA-Fc) and Luspatercept (modified ActRIIB-Fc), 
have the potential for being misused as doping agents in sports as they were 
found to inhibit negative regulators of late-stage erythropoiesis. Within this 
study, ammonium sulfate precipitation, immunoaffinity purification, tryptic 
digestion, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were 
employed to develop an assay for the combined detection of Sotatercept and 
Luspatercept in doping control serum samples. The assay was optimized, 
comprehensively characterized, and found to be fit-for-purpose for application 
to sports drug testing. It complements existing tests for ActRII-Fc fusion 
proteins and expands the range of available detection methods for novel protein 
therapeutics.