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Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma
Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract can...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028559/ https://www.ncbi.nlm.nih.gov/pubmed/35458589 http://dx.doi.org/10.3390/molecules27082394 |
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author | Schwarz, Rico Richter, Anna Ito, Elisabeth R. D. Murua Escobar, Hugo Junghanß, Christian Hinz, Burkhard |
author_facet | Schwarz, Rico Richter, Anna Ito, Elisabeth R. D. Murua Escobar, Hugo Junghanß, Christian Hinz, Burkhard |
author_sort | Schwarz, Rico |
collection | PubMed |
description | Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract cancer. Silmitasertib inhibits the serine/threonine protein kinase CK2, which exerts a proliferation-promoting and anti-apoptotic effect on cancer cells. In view of current and future applications, the measurement of silmitasertib levels in plasma is expected to play an important role in the evaluation of therapeutic and toxic concentrations in cancer patients. In the present work, we therefore present an LC–MS/MS method for the quantification of silmitasertib in human plasma. Using a simple liquid–liquid extraction with ethyl acetate and a mixture of n-hexane and ethyl acetate, this method can be performed in any laboratory with mass spectrometry. The validation was carried out according to the FDA guideline. |
format | Online Article Text |
id | pubmed-9028559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90285592022-04-23 Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma Schwarz, Rico Richter, Anna Ito, Elisabeth R. D. Murua Escobar, Hugo Junghanß, Christian Hinz, Burkhard Molecules Article Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract cancer. Silmitasertib inhibits the serine/threonine protein kinase CK2, which exerts a proliferation-promoting and anti-apoptotic effect on cancer cells. In view of current and future applications, the measurement of silmitasertib levels in plasma is expected to play an important role in the evaluation of therapeutic and toxic concentrations in cancer patients. In the present work, we therefore present an LC–MS/MS method for the quantification of silmitasertib in human plasma. Using a simple liquid–liquid extraction with ethyl acetate and a mixture of n-hexane and ethyl acetate, this method can be performed in any laboratory with mass spectrometry. The validation was carried out according to the FDA guideline. MDPI 2022-04-07 /pmc/articles/PMC9028559/ /pubmed/35458589 http://dx.doi.org/10.3390/molecules27082394 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Schwarz, Rico Richter, Anna Ito, Elisabeth R. D. Murua Escobar, Hugo Junghanß, Christian Hinz, Burkhard Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma |
title | Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma |
title_full | Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma |
title_fullStr | Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma |
title_full_unstemmed | Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma |
title_short | Validation of an LC–MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma |
title_sort | validation of an lc–ms/ms method for the quantification of the ck2 inhibitor silmitasertib (cx-4945) in human plasma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028559/ https://www.ncbi.nlm.nih.gov/pubmed/35458589 http://dx.doi.org/10.3390/molecules27082394 |
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