Intact plasma quantification of the large therapeutic lipopeptide bulevirtide

• Verfasst von: Sauter, Max [VerfasserIn]
• Verfasst von: Blank, Antje [VerfasserIn]
• Verfasst von: Stoll, Felicitas E. [VerfasserIn]
• Verfasst von: Lutz, Natalie [VerfasserIn]
• Verfasst von: Haefeli, Walter E. [VerfasserIn]
• Verfasst von: Burhenne, Jürgen [VerfasserIn]
• Titel: Intact plasma quantification of the large therapeutic lipopeptide bulevirtide
• Verf.angabe: Max Sauter, Antje Blank, Felicitas Stoll, Natalie Lutz, Walter E. Haefeli, Jürgen Burhenne
• E-Jahr: 2021
• Jahr: 20 May 2021
• Umfang: 10 S.
• Fussnoten: Gesehen am 18.09.2023
• Titel Quelle: Enthalten in: Analytical and bioanalytical chemistry
• Ort Quelle: Berlin : Springer, 2002
• Jahr Quelle: 2021
• Band/Heft Quelle: 413(2021), 22, Seite 5645-5654
• ISSN Quelle: 1618-2650
• DOI: doi:10.1007/s00216-021-03384-7
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1859837603
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Bulevirtide is a first-in-class entry inhibitor of the hepatitis B and hepatitis delta virus blocking the sodium/bile acid co-transporter NTCP, and was recently approved for the treatment of hepatitis D as a priority medicine (prime) in an accelerated assessment by the European Medicines Agency. It is a very large lipopeptide comprising 47 amino acids in its sequence and a myristoylation at the N-terminus. For support of clinical development, we established highly sensitive plasma quantification assays using 100 μL of plasma, spanning concentrations of 0.1 to 100 ng/mL and 1 to 1000 ng/mL with the option to measure ten-fold diluted samples up to 10,000 ng/mL. Quantification was performed with UPLC-MS/MS measurements after extraction with protein precipitation. Both assays were fully validated according to the pertinent guidelines of the FDA and EMA, including incurred sample reanalyses and cross-validation using clinical study samples.