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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0259137 |
| _version_ | 1819176034733391872 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T21:04:21Z |
| format | Article |
| id | doaj.art-b7f52d55ed6e42d188d408f4a394726d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T21:04:21Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b7f52d55ed6e42d188d408f4a394726d2022-12-21T18:12:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011610e025913710.1371/journal.pone.0259137A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring.Martina ZanchettaValentina IacuzziBianca PosoccoGiorgia BortolinAriana Soledad PoettoMarco OrleniGiovanni CanilMichela GuardascioneLuisa FoltranValentina FanottoFabio PuglisiSara GagnoGiuseppe ToffoliLenvatinib (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.https://doi.org/10.1371/journal.pone.0259137 |
| spellingShingle | 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. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0259137 |
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