Evidence map›Paper›PMID 39297399›Full record

ArticleEpilepsia open2024

A VAMS-based LC-MS/MS method for precise cenobamate quantification in epilepsy (patients).

Federica Pigliasco, Alessia Cafaro, Sebastiano Barco, Margherita Biondi, Manuela Stella, Francesca Mattioli, Antonella Riva, Ugo de Grazia, Linda Molteni, Elisa Micalizzi and 4 more

Abstract read
In one paragraph

Article in Epilepsia open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Modern Analytical Techniques in Epilepsy Research.International journal of molecular sciences · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Federica PigliascoChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.ORCID https://orcid.org/0000-0002-2631-8610
Alessia CafaroChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.ORCID https://orcid.org/0000-0003-1132-1267
Sebastiano BarcoChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Margherita BiondiChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Manuela StellaIRCCS Istituto Giannina Gaslini, Gaslini Trial Centre, Genova, Italy.
Francesca MattioliPharmacology and Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Antonella RivaDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Ugo de GraziaSSD Laboratory Medicine - SMEL122, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Linda MolteniSSD Laboratory Medicine - SMEL122, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.ORCID https://orcid.org/0000-0003-0915-5597
Elisa MicalizziClinical Neurophysiology Unit and Epilepsy Center, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Flavio VillaniClinical Neurophysiology Unit and Epilepsy Center, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Pasquale StrianoDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.ORCID https://orcid.org/0000-0002-6065-1476
Roberto BandettiniChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Giuliana CangemiChromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Funding

5 × 1000 in support of Health ResearchItalian Ministry of Health RC2023PNRR-MUR-M4C2 PE0000006 Research Program "MNESYS"-A multiscale integrated approach to the study of the nervous system in health and disease
6 · The paper itself

Abstract

objectiveCenobamate (CNB), a recently approved antiseizure medication by the European Medicines Agency (EMA), serves as an adjunctive therapy for focal-onset seizures in adult patients unresponsive to at least two other treatments. Administered in polytherapy, CNB can potentially interact with co-administered drugs in epilepsy patients, necessitating dose adjustments and the need for effective therapeutic drug monitoring (TDM).

methodsIn this study, we introduce a novel LC-MS/MS method for precise CNB quantification using Volumetric Absorptive Microsampling (VAMS), following validation according to ICH guidelines M10. VAMS samples are efficiently extracted with 200 μL of methanol, with chromatographic separation achieved using an Acquity UPLC HSS PFP column. The method's efficacy was confirmed through its application to real samples from adult CNB-treated patients.

resultsOur results demonstrate that the method exhibits linearity within the range of 0.05-30 mg/L, with intra- and inter-run precision ranging from 1% to 8% and accuracy from 1% to 10% based on 30 μL of sample. Furthermore, CNB stability in VAMS is confirmed for up to 15 days at 25°C and -20°C. Importantly, no significant difference was observed between CNB concentrations in VAMS samples and those in plasma obtained from venous blood. SIGNIFICANCE: This VAMS-based LC-MS/MS method presents a robust alternative for TDM in CNB-treated patients. Future investigations should explore CNB concentrations in capillary blood and assess their correlation with plasma levels to further enhance its clinical utility. PLAIN LANGUAGE SUMMARY: Cenobamate is an antiepileptic drug and used for treatment of focal-onset seizures in adult patients (≥18 age). TDM can prevent drug interactions and minimize drug toxicity. The aim of this work is to evaluate volumetric absorptive microsampling (VAMS) from capillary blood as an alternative strategy for TDM in patients treated with the newly antiepileptic drug. Our method is suitable for TDM, and this study suggests that VAMS allows monitoring of cenobamate concentration and can offer valuable support for personalized therapy in refractory epilepsy.

Indexed as

AnticonvulsantsCarbamatesDrug MonitoringEpilepsyTandem Mass SpectrometryAdultChlorophenolsChromatography, LiquidFemaleHumansLiquid Chromatography-Mass SpectrometryMaleReproducibility of ResultsTetrazolesAnticonvulsantsCarbamatesCenobamateChlorophenolsTetrazolesantiseizure medicationscenobamatedrug monitoringliquid chromatography tandem‐mass spectrometryvolumetric absorptive microsampling

Identifiers

PMID39297399
PMCPMC11633685

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.