{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T04:56:53Z","timestamp":1769576213711,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PhD fellowship from FCT"},{"name":"National Funds from Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) under the scope of PORTUGAL 2020 and Programa Operacional do Centro (CENTRO 2020)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Epilepsy affects approximately 50 million people worldwide, with antiepileptic drugs (AEDs) remaining the cornerstone of treatment. Due to their narrow therapeutic windows, AEDs are ideal candidates for therapeutic drug monitoring (TDM). Oral fluid is increasingly considered a viable alternative to blood and urine, as it reflects the free (active) concentration of many AEDs. Its non-invasive collection, which does not require trained personnel, makes it particularly suitable for TDM in paediatric and geriatric populations. However, as samples are often stored for extended periods before analysis, analyte stability becomes a critical concern. This study aimed to evaluate the stability of four commonly used AEDs in dried saliva spot (DSS) samples. Methods: Phenobarbital, phenytoin, carbamazepine, and carbamazepine-10,11-epoxide were analysed in oral fluid samples collected via spitting and stored as DSSs. Quantification was performed using high-performance liquid chromatography with diode array detection (HPLC-DAD). Design of experiments tools were used to assess the effects of preservatives, storage temperatures, light exposure, and storage durations on analyte stability. Results: Optimal conditions were refrigeration in the dark, with a low concentration of ascorbic acid as preservative. Samples at 10 \u00b5g\/mL remained stable for 14 days longer than those without preservative or reported in previous studies. Unexpectedly, at 0.5 \u00b5g\/mL, analytes in samples without preservative showed greater stability. Conclusions: To our knowledge, this is the first study combining DSS and HPLC-DAD to assess the stability of these AEDs in oral fluid, providing valuable insights for non-invasive TDM strategies and supporting the feasibility of saliva-based monitoring in clinical settings.<\/jats:p>","DOI":"10.3390\/ph18071049","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:33:47Z","timestamp":1752748427000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Antiepileptic Drugs\u2019 Stability in Oral Fluid Samples"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8014-3643","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Martinho","sequence":"first","affiliation":[{"name":"RISE-Health, Departamento de Ci\u00eancias M\u00e9dicas, Faculdade de Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3199-1866","authenticated-orcid":false,"given":"Ana Y.","family":"Sim\u00e3o","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Ci\u00eancias M\u00e9dicas, Faculdade de Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0469-2895","authenticated-orcid":false,"given":"Tiago","family":"Rosado","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Ci\u00eancias M\u00e9dicas, Faculdade de Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"},{"name":"Centro Acad\u00e9mico Cl\u00ednico das Beiras (CACB), Grupo de Problemas Relacionados com Toxicofilias, UBIMedical, Universidade da Beira Interior, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-8998","authenticated-orcid":false,"given":"Eugenia","family":"Gallardo","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Ci\u00eancias M\u00e9dicas, Faculdade de Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laborat\u00f3rio de F\u00e1rmaco-Toxicologia-UBIMedical, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"},{"name":"Centro Acad\u00e9mico Cl\u00ednico das Beiras (CACB), Grupo de Problemas Relacionados com Toxicofilias, UBIMedical, Universidade da Beira Interior, Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1055\/s-0040-1718719","article-title":"Epilepsy-Definition, Classification, Pathophysiology, and Epidemiology","volume":"40","year":"2020","journal-title":"Semin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1055\/s-0038-1646947","article-title":"Global Health: Epilepsy","volume":"38","author":"Ali","year":"2018","journal-title":"Semin. 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