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A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring
Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantif...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547652/ https://www.ncbi.nlm.nih.gov/pubmed/34699578 http://dx.doi.org/10.1371/journal.pone.0259137 |
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author | Zanchetta, Martina Iacuzzi, Valentina Posocco, Bianca Bortolin, Giorgia Poetto, Ariana Soledad Orleni, Marco Canil, Giovanni Guardascione, Michela Foltran, Luisa Fanotto, Valentina Puglisi, Fabio Gagno, Sara Toffoli, Giuseppe |
author_facet | Zanchetta, Martina Iacuzzi, Valentina Posocco, Bianca Bortolin, Giorgia Poetto, Ariana Soledad Orleni, Marco Canil, Giovanni Guardascione, Michela Foltran, Luisa Fanotto, Valentina Puglisi, Fabio Gagno, Sara Toffoli, Giuseppe |
author_sort | Zanchetta, Martina |
collection | PubMed |
description | Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantification method to be applied in the clinical setting is essential. The aim of this work was to develop and validate a sensitive, rapid, and cost-effective LC-MS/MS method for the quantification of LENVA in human plasma. On this premise, sample preparation was based on a protein precipitation and the chromatographic separation was achieved on a Synergi Fusion RP C18 column in 4 min. The method was completely and successfully validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, with good linearity in the range of 0.50–2000 ng/mL (R≥0.9968). Coefficient of variation (CV) for intra- and inter-day precision was ≤11.3% and accuracy ranged from 96.3 to 109.0%, internal standard normalized matrix effect CV% was ≤2.8% and recovery was ≥95.6%. Successful results were obtained for sensitivity (signal to noise (S/N) ratio >21) and selectivity, dilution integrity (CV% ≤ 4.0% and accuracy 99.9–102%), and analyte stability under various handling and storage conditions both in matrix and solvents. This method was applied to quantify LENVA in patient’s plasma samples and covered the concentration range achievable in patients. In conclusion, a sensitive and robust quantification method was developed and validated to be applied in the clinical setting. |
format | Online Article Text |
id | pubmed-8547652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-85476522021-10-27 A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring Zanchetta, Martina Iacuzzi, Valentina Posocco, Bianca Bortolin, Giorgia Poetto, Ariana Soledad Orleni, Marco Canil, Giovanni Guardascione, Michela Foltran, Luisa Fanotto, Valentina Puglisi, Fabio Gagno, Sara Toffoli, Giuseppe PLoS One Research Article Lenvatinib (LENVA) is an oral antineoplastic drug used for the treatment of hepatocellular carcinoma and thyroid carcinoma. LENVA therapeutic drug monitoring (TDM) should be mandatory for a precision medicine to optimize the drug dosage. To this end, the development of a sensitive and robust quantification method to be applied in the clinical setting is essential. The aim of this work was to develop and validate a sensitive, rapid, and cost-effective LC-MS/MS method for the quantification of LENVA in human plasma. On this premise, sample preparation was based on a protein precipitation and the chromatographic separation was achieved on a Synergi Fusion RP C18 column in 4 min. The method was completely and successfully validated according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines, with good linearity in the range of 0.50–2000 ng/mL (R≥0.9968). Coefficient of variation (CV) for intra- and inter-day precision was ≤11.3% and accuracy ranged from 96.3 to 109.0%, internal standard normalized matrix effect CV% was ≤2.8% and recovery was ≥95.6%. Successful results were obtained for sensitivity (signal to noise (S/N) ratio >21) and selectivity, dilution integrity (CV% ≤ 4.0% and accuracy 99.9–102%), and analyte stability under various handling and storage conditions both in matrix and solvents. This method was applied to quantify LENVA in patient’s plasma samples and covered the concentration range achievable in patients. In conclusion, a sensitive and robust quantification method was developed and validated to be applied in the clinical setting. Public Library of Science 2021-10-26 /pmc/articles/PMC8547652/ /pubmed/34699578 http://dx.doi.org/10.1371/journal.pone.0259137 Text en © 2021 Zanchetta et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zanchetta, Martina Iacuzzi, Valentina Posocco, Bianca Bortolin, Giorgia Poetto, Ariana Soledad Orleni, Marco Canil, Giovanni Guardascione, Michela Foltran, Luisa Fanotto, Valentina Puglisi, Fabio Gagno, Sara Toffoli, Giuseppe A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
title | A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
title_full | A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
title_fullStr | A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
title_full_unstemmed | A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
title_short | A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
title_sort | rapid, simple and sensitive lc-ms/ms method for lenvatinib quantification in human plasma for therapeutic drug monitoring |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547652/ https://www.ncbi.nlm.nih.gov/pubmed/34699578 http://dx.doi.org/10.1371/journal.pone.0259137 |
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