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Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS
A sensitive and selective ultra‐high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous determination of seven oral oncolytics (two PARP inhibitors, i.e. olaparib and niraparib, and five tyrosine kinase inhibitors, i.e. cobimetinib, cabozantinib, dabr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065026/ https://www.ncbi.nlm.nih.gov/pubmed/31758580 http://dx.doi.org/10.1002/bmc.4758 |
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author | Krens, Stefanie D. van der Meulen, Eric Jansman, Frank G.A. Burger, David M. van Erp, Nielka P. |
author_facet | Krens, Stefanie D. van der Meulen, Eric Jansman, Frank G.A. Burger, David M. van Erp, Nielka P. |
author_sort | Krens, Stefanie D. |
collection | PubMed |
description | A sensitive and selective ultra‐high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous determination of seven oral oncolytics (two PARP inhibitors, i.e. olaparib and niraparib, and five tyrosine kinase inhibitors, i.e. cobimetinib, cabozantinib, dabrafenib, vemurafenib and regorafenib, plus its active metabolite regorafenib M2) in EDTA plasma was developed and validated. Stable isotope‐labelled internal standards were used for each analyte. A simple protein precipitation method was performed with acetonitrile. The LC–MS/MS system consisted of an Acquity H‐Class UPLC system, coupled to a Xevo TQ‐S micro tandem mass spectrometer. The compounds were separated on a Waters CORTECS UPLC C18 column (2.1 × 50 mm, 1.6 μm particle size) and eluted with a gradient elution system. The ions were detected in the multiple reaction monitoring mode. The method was validated for cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and regorafenib M2 over the ranges 6–1000, 100–5000, 10–4000, 200–2000, 200–20,000, 5000–100,000, 500–10,000 and 500–10,000 μg/L, respectively. Within‐day accuracy values for all analytes ranged from 86.8 to 115.0% with a precision of <10.4%. Between‐day accuracy values ranged between 89.7 and 111.9% with a between‐day precision of <7.4%. The developed method was successfully used for guiding therapy with therapeutic drug monitoring in cancer patients and clinical research programs in our laboratory. |
format | Online Article Text |
id | pubmed-7065026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70650262020-03-16 Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS Krens, Stefanie D. van der Meulen, Eric Jansman, Frank G.A. Burger, David M. van Erp, Nielka P. Biomed Chromatogr Research Articles A sensitive and selective ultra‐high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous determination of seven oral oncolytics (two PARP inhibitors, i.e. olaparib and niraparib, and five tyrosine kinase inhibitors, i.e. cobimetinib, cabozantinib, dabrafenib, vemurafenib and regorafenib, plus its active metabolite regorafenib M2) in EDTA plasma was developed and validated. Stable isotope‐labelled internal standards were used for each analyte. A simple protein precipitation method was performed with acetonitrile. The LC–MS/MS system consisted of an Acquity H‐Class UPLC system, coupled to a Xevo TQ‐S micro tandem mass spectrometer. The compounds were separated on a Waters CORTECS UPLC C18 column (2.1 × 50 mm, 1.6 μm particle size) and eluted with a gradient elution system. The ions were detected in the multiple reaction monitoring mode. The method was validated for cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and regorafenib M2 over the ranges 6–1000, 100–5000, 10–4000, 200–2000, 200–20,000, 5000–100,000, 500–10,000 and 500–10,000 μg/L, respectively. Within‐day accuracy values for all analytes ranged from 86.8 to 115.0% with a precision of <10.4%. Between‐day accuracy values ranged between 89.7 and 111.9% with a between‐day precision of <7.4%. The developed method was successfully used for guiding therapy with therapeutic drug monitoring in cancer patients and clinical research programs in our laboratory. John Wiley and Sons Inc. 2020-01-13 2020-03 /pmc/articles/PMC7065026/ /pubmed/31758580 http://dx.doi.org/10.1002/bmc.4758 Text en © 2019 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Krens, Stefanie D. van der Meulen, Eric Jansman, Frank G.A. Burger, David M. van Erp, Nielka P. Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS |
title | Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS |
title_full | Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS |
title_fullStr | Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS |
title_full_unstemmed | Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS |
title_short | Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS |
title_sort | quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib m2 in human plasma by uplc–ms/ms |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065026/ https://www.ncbi.nlm.nih.gov/pubmed/31758580 http://dx.doi.org/10.1002/bmc.4758 |
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