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:	Martina Zanchetta, Valentina Iacuzzi, Bianca Posocco, Giorgia Bortolin, Ariana Soledad Poetto, Marco Orleni, Giovanni Canil, Michela Guardascione, Luisa Foltran, Valentina Fanotto, Fabio Puglisi, Sara Gagno, Giuseppe Toffoli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b7f52d55ed6e42d188d408f4a394726d
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spelling	oai:doaj.org-article:b7f52d55ed6e42d188d408f4a394726d2021-12-02T20:13:28ZA rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring.1932-620310.1371/journal.pone.0259137https://doaj.org/article/b7f52d55ed6e42d188d408f4a394726d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259137https://doaj.org/toc/1932-6203Lenvatinib (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.Martina ZanchettaValentina IacuzziBianca PosoccoGiorgia BortolinAriana Soledad PoettoMarco OrleniGiovanni CanilMichela GuardascioneLuisa FoltranValentina FanottoFabio PuglisiSara GagnoGiuseppe ToffoliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0259137 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martina Zanchetta Valentina Iacuzzi Bianca Posocco Giorgia Bortolin Ariana Soledad Poetto Marco Orleni Giovanni Canil Michela Guardascione Luisa Foltran Valentina Fanotto Fabio Puglisi Sara Gagno Giuseppe Toffoli A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring.
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	article
author	Martina Zanchetta Valentina Iacuzzi Bianca Posocco Giorgia Bortolin Ariana Soledad Poetto Marco Orleni Giovanni Canil Michela Guardascione Luisa Foltran Valentina Fanotto Fabio Puglisi Sara Gagno Giuseppe Toffoli
author_facet	Martina Zanchetta Valentina Iacuzzi Bianca Posocco Giorgia Bortolin Ariana Soledad Poetto Marco Orleni Giovanni Canil Michela Guardascione Luisa Foltran Valentina Fanotto Fabio Puglisi Sara Gagno Giuseppe Toffoli
author_sort	Martina Zanchetta
title	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_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_sort	rapid, simple and sensitive lc-ms/ms method for lenvatinib quantification in human plasma for therapeutic drug monitoring.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b7f52d55ed6e42d188d408f4a394726d
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A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring.

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