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Intact plasma quantification of the large therapeutic lipopeptide bulevirtide
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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410713/ https://www.ncbi.nlm.nih.gov/pubmed/34018034 http://dx.doi.org/10.1007/s00216-021-03384-7 |
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author | Sauter, Max Blank, Antje Stoll, Felicitas Lutz, Natalie Haefeli, Walter E. Burhenne, Jürgen |
author_facet | Sauter, Max Blank, Antje Stoll, Felicitas Lutz, Natalie Haefeli, Walter E. Burhenne, Jürgen |
author_sort | Sauter, Max |
collection | PubMed |
description | 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. [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00216-021-03384-7. |
format | Online Article Text |
id | pubmed-8410713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-84107132021-09-22 Intact plasma quantification of the large therapeutic lipopeptide bulevirtide Sauter, Max Blank, Antje Stoll, Felicitas Lutz, Natalie Haefeli, Walter E. Burhenne, Jürgen Anal Bioanal Chem Research Paper 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. [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00216-021-03384-7. Springer Berlin Heidelberg 2021-05-20 2021 /pmc/articles/PMC8410713/ /pubmed/34018034 http://dx.doi.org/10.1007/s00216-021-03384-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Paper Sauter, Max Blank, Antje Stoll, Felicitas Lutz, Natalie Haefeli, Walter E. Burhenne, Jürgen Intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
title | Intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
title_full | Intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
title_fullStr | Intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
title_full_unstemmed | Intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
title_short | Intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
title_sort | intact plasma quantification of the large therapeutic lipopeptide bulevirtide |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410713/ https://www.ncbi.nlm.nih.gov/pubmed/34018034 http://dx.doi.org/10.1007/s00216-021-03384-7 |
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