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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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