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Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples

Cenobamate (CNB) is the newest antiseizure medication (ASM) approved by the FDA in 2019 to reduce uncontrolled partial-onset seizures in adult patients. Marketed as Xcopri in the USA or Ontozry in the EU (tablets), its mechanism of action has not been fully understood yet; however, it is known that...

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Autores principales: Charlier, Bruno, Coglianese, Albino, Operto, Francesca Felicia, Coppola, Giangennaro, de Grazia, Ugo, Menna, Pierantonio, Filippelli, Amelia, Dal Piaz, Fabrizio, Izzo, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656984/
https://www.ncbi.nlm.nih.gov/pubmed/36364153
http://dx.doi.org/10.3390/molecules27217325
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author Charlier, Bruno
Coglianese, Albino
Operto, Francesca Felicia
Coppola, Giangennaro
de Grazia, Ugo
Menna, Pierantonio
Filippelli, Amelia
Dal Piaz, Fabrizio
Izzo, Viviana
author_facet Charlier, Bruno
Coglianese, Albino
Operto, Francesca Felicia
Coppola, Giangennaro
de Grazia, Ugo
Menna, Pierantonio
Filippelli, Amelia
Dal Piaz, Fabrizio
Izzo, Viviana
author_sort Charlier, Bruno
collection PubMed
description Cenobamate (CNB) is the newest antiseizure medication (ASM) approved by the FDA in 2019 to reduce uncontrolled partial-onset seizures in adult patients. Marketed as Xcopri in the USA or Ontozry in the EU (tablets), its mechanism of action has not been fully understood yet; however, it is known that it inhibits voltage-gated sodium channels and positively modulates the aminobutyric acid (GABA) ion channel. CNB shows 88% of oral bioavailability and is responsible for modifying the plasma concentrations of other co-administered ASMs, such as lamotrigine, carbamazepine, phenytoin, phenobarbital and the active metabolite of clobazam. It also interferes with CYP2B6 and CYP3A substrates. Nowadays, few methods are reported in the literature to quantify CNB in human plasma. The aim of this study was to develop and validate, according to the most recent guidelines, an analytical method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) to evaluate CNB dosage in plasma samples. Furthermore, we provided a preliminary clinical application of our methodology by evaluating the pharmacokinetic parameters of CNB in two non-adult patients. Plasma levels were monitored for two months. Preliminary data showed a linear increase in plasma CNB concentrations, in both patients, in agreement with the increase in CNB dosage. A seizure-free state was reported for both patients at the dose of 150 mg per day.
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spelling pubmed-96569842022-11-15 Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples Charlier, Bruno Coglianese, Albino Operto, Francesca Felicia Coppola, Giangennaro de Grazia, Ugo Menna, Pierantonio Filippelli, Amelia Dal Piaz, Fabrizio Izzo, Viviana Molecules Article Cenobamate (CNB) is the newest antiseizure medication (ASM) approved by the FDA in 2019 to reduce uncontrolled partial-onset seizures in adult patients. Marketed as Xcopri in the USA or Ontozry in the EU (tablets), its mechanism of action has not been fully understood yet; however, it is known that it inhibits voltage-gated sodium channels and positively modulates the aminobutyric acid (GABA) ion channel. CNB shows 88% of oral bioavailability and is responsible for modifying the plasma concentrations of other co-administered ASMs, such as lamotrigine, carbamazepine, phenytoin, phenobarbital and the active metabolite of clobazam. It also interferes with CYP2B6 and CYP3A substrates. Nowadays, few methods are reported in the literature to quantify CNB in human plasma. The aim of this study was to develop and validate, according to the most recent guidelines, an analytical method using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) to evaluate CNB dosage in plasma samples. Furthermore, we provided a preliminary clinical application of our methodology by evaluating the pharmacokinetic parameters of CNB in two non-adult patients. Plasma levels were monitored for two months. Preliminary data showed a linear increase in plasma CNB concentrations, in both patients, in agreement with the increase in CNB dosage. A seizure-free state was reported for both patients at the dose of 150 mg per day. MDPI 2022-10-28 /pmc/articles/PMC9656984/ /pubmed/36364153 http://dx.doi.org/10.3390/molecules27217325 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Charlier, Bruno
Coglianese, Albino
Operto, Francesca Felicia
Coppola, Giangennaro
de Grazia, Ugo
Menna, Pierantonio
Filippelli, Amelia
Dal Piaz, Fabrizio
Izzo, Viviana
Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples
title Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples
title_full Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples
title_fullStr Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples
title_full_unstemmed Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples
title_short Development and Validation of a UHPLC–MS/MS-Based Method to Quantify Cenobamate in Human Plasma Samples
title_sort development and validation of a uhplc–ms/ms-based method to quantify cenobamate in human plasma samples
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656984/
https://www.ncbi.nlm.nih.gov/pubmed/36364153
http://dx.doi.org/10.3390/molecules27217325
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