{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:38Z","timestamp":1786977158797,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["009\/2024"],"award-info":[{"award-number":["009\/2024"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["429728\/2018\u20102"],"award-info":[{"award-number":["429728\/2018\u20102"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glioblastoma multiforme (GBM) is among the most aggressive brain tumors, largely due to the restrictive blood\u2013brain barrier (BBB) and limited drug bioavailability. Temozolomide (TMZ), an alkylating agent, and perillyl alcohol (POH), a monoterpene with antitumor properties, have shown promise in GBM therapy. This study developed and validated a UPLC\u2010MS\/MS method for the simultaneous quantification of TMZ, its active metabolite 5\u2010aminoimidazole\u20104\u2010carboxamide (AIC), and perillic acid (PA), the primary POH metabolite, in rat plasma and tissues. The method met FDA and EMA validation criteria, showing high selectivity, linearity (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009&gt;\u20090.995), accuracy (80%\u2013120%), precision (RSD\u2009&lt;\u200915%), and matrix\u2010specific stability across plasma, brain, liver, kidney, spleen, and lung. Following single oral doses of TMZ (2\u2009mg\/kg) and POH (47\u2009mg\/kg), pharmacokinetic analysis revealed that TMZ had the highest systemic exposure (AUC\n                    <jats:sub>0\u201324h<\/jats:sub>\n                    : 8173.64\u2009ng\u00b7h\/mL) and C\n                    <jats:sub>max<\/jats:sub>\n                    (1448.64\u2009ng\/mL), while PA showed the fastest absorption (t\n                    <jats:sub>max<\/jats:sub>\n                    : 0.5\u2009h). AIC levels confirmed efficient TMZ metabolism. Biodistribution analysis showed TMZ accumulation in the brain (~1000\u2009ng\/mL), supporting its CNS efficacy. PA was mainly distributed to liver and kidneys, with limited brain penetration. The validated method enables preclinical pharmacokinetic and tissue distribution studies, offering valuable insights into TMZ and POH behavior for GBM treatment.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70253","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T12:40:22Z","timestamp":1763556022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Validated UPLC\u2010MS\/MS Method for Monitoring Temozolomide and Perillyl Alcohol Metabolites in Biological Matrices: Insights From a Preclinical Pharmacokinetic Study"],"prefix":"10.1002","volume":"39","author":[{"given":"Ariane\u00a0Krause\u00a0Padilha","family":"Lorenzett","sequence":"first","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane\u00a0Patricia","family":"Babinski","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samila\u00a0Horst","family":"Peczek","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00a0Paula","family":"Tartari","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeferson","family":"Ziebarth","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa","family":"Zago","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais\u00a0Carla\u00a0Brussulo","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4442-2075","authenticated-orcid":false,"given":"Rubiana\u00a0Mara","family":"Mainardes","sequence":"additional","affiliation":[{"name":"Laboratory of Nanostructured Formulations Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"},{"name":"Department of Pharmacy Universidade Estadual do Centro\u2010Oeste  Guarapuava Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.33218\/001c.17880"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES24234312"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13122167"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201012\u20100321\/84642\/AM\/PERILLYL\u2010ALCOHOL\u2010POH\u2010FOR\u2010THE\u2010TREATMENT\u2010OF"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/2152\u20107806.173301"},{"key":"e_1_2_10_7_1","unstructured":"European Medicines Agency (EMA).2021. \u201cBioanalytical Method Validation\u2014Scientific Guideline.\u201dhttps:\/\/www.ema.europa.eu\/en\/bioanalytical\u2010method\u2010validation\u2010scientific\u2010guideline."},{"issue":"7","key":"e_1_2_10_8_1","first-page":"2585","article-title":"Temozolomide and Treatment of Malignant Glioma","volume":"6","author":"Friedman H. 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