Combined detection of the ActRII‐Fc fusion proteins Sotatercept (ActRIIA‐Fc) and Luspatercept (modified ActRIIB‐Fc) in serum by means of immunoaffinity purification, tryptic digestion, and LC‐MS/MS
Deutscher übersetzter Titel: | Kombinierter Nachweis der ActRII‐Fc Fusionsproteine Sotatercept (ActRIIA‐Fc) und Luspatercept (modifiziertes ActRIIB‐Fc) im Blutserum durch Immun-Affinitätspurifikation, tryptische Digestion und LC‐MS/MS |
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Autor: | Walpurgis, Katja; Thomas, Andreas; Lange, Tobias; Reichel, Christian; Geyer, Hans; Thevis, Mario |
Erschienen in: | Drug testing and analysis |
Veröffentlicht: | 10 (2018), 11/12 (36th Cologne workshop: Advances in sports drug testing), S. 1714-1721, Lit. |
Format: | Literatur (SPOLIT) |
Publikationstyp: | Zeitschriftenartikel |
Medienart: | Elektronische Ressource (online) Gedruckte Ressource |
Sprache: | Englisch |
ISSN: | 1942-7603, 1942-7611 |
DOI: | 10.1002/dta.2513 |
Schlagworte: | |
Online Zugang: | |
Erfassungsnummer: | PU202011010166 |
Quelle: | BISp |
Abstract des Autors
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.