{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:18:48Z","timestamp":1780319928382,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-Next GenerationEU","award":["15204"],"award-info":[{"award-number":["15204"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Anxiety and stress-related disorders affect all ages in all geographical areas. As high anxiety and chronic stress result in the modulation of mitochondrial pathways, intensive research is being carried out on pharmaceutical interventions that alleviate pertinent symptomatology. Therefore, innovative approaches being currently pursued include substances that target mitochondria bearing an antioxidant moiety. In this study, a newly synthesized antioxidant consisting of triphenylphosphine (TPP), a six-carbon alkyl spacer, and hydroxytyrosol (HT) was administered orally to mice via drinking water. Cerebellum and liver samples were collected and analyzed using ultra-high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-MS\/MS) to assess the levels of TPP-HT in the respective tissues to evaluate in vivo administration efficacy. Sample preparation included extraction with appropriate solvents and a preconcentration step to achieve the required sensitivity. Both methods were validated in terms of selectivity, linearity, accuracy, and limits of detection and quantification. Additionally, a workflow for evaluating and statistically summarizing multiple fortified calibration curves was devised. TPP-HT penetrates the blood\u2013brain barrier (BBB), with a level of 11.5 ng g\u22121 quantified in the cerebellum, whereas a level of 4.8 ng g\u22121 was detected in the liver, highlighting the plausibility of orally administering TPP-HT to achieve mitochondrial targeting.<\/jats:p>","DOI":"10.3390\/molecules30091900","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T10:17:16Z","timestamp":1745489836000},"page":"1900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liquid Chromatography-Tandem Mass Spectrometry Method Development and Validation for the Determination of a New Mitochondrial Antioxidant in Mouse Liver and Cerebellum, Employing Advanced Chemometrics"],"prefix":"10.3390","volume":"30","author":[{"given":"Anthi","family":"Panara","sequence":"first","affiliation":[{"name":"Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Biliraki","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Nussbaumer","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology-Hellas, 45100 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela D.","family":"Filiou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology-Hellas, 45100 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4624-4735","authenticated-orcid":false,"given":"Nikolaos S.","family":"Thomaidis","sequence":"additional","affiliation":[{"name":"Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9901-5223","authenticated-orcid":false,"given":"Ioannis K.","family":"Kostakis","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-9991","authenticated-orcid":false,"given":"Evagelos","family":"Gikas","sequence":"additional","affiliation":[{"name":"Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","unstructured":"(2024, October 06). 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