{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:42:24Z","timestamp":1790862144335,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T00:00:00Z","timestamp":1745107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methylene blue (MB), a phenothiazine derivative, is currently under clinical trials for Alzheimer's disease (\n                    <jats:sc>AD<\/jats:sc>\n                    ) due to its potential to inhibit tau aggregation, a key pathological process in\n                    <jats:sc>AD<\/jats:sc>\n                    . In this study, we developed and qualified a rapid and reliable liquid chromatography\u2010quadrupole time\u2010of\u2010flight mass spectrometry (LC\u2010qTOF\u2010MS) method for the quantification of MB in mouse plasma and brain samples. Chromatographic separation was achieved using a PolymerX RP\u20101 100\u2009\u00c5 (50\u2009\u00d7\u20092\u2009mm, 5\u2009\u03bcm) column with a mobile phase consisting of water and methanol containing 0.5% difluoroacetic acid, delivered at a flow rate of 0.5\u2009mL\/min. Calibration curves were constructed using quadratic regression (weighted 1\/concentration\n                    <jats:sup>2<\/jats:sup>\n                    ) over a range of 3.05\u20132222.22\u2009ng\/mL in both matrices. The method was successfully applied to characterize the pharmacokinetics of MB in male ICR mice, revealing a high systemic clearance (65.64\u2009mL\/min\/kg) and substantial brain penetration, as indicated by a brain\u2010to\u2010plasma partition coefficient (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>p,brain<\/jats:italic>\n                    <\/jats:sub>\n                    ) of 23.50 following single intravenous bolus administration. These findings provide critical insights into MB's in\u00a0vivo behavior and demonstrate the utility of this bioanalytical method for evaluating MB in preclinical studies.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70080","type":"journal-article","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T22:35:36Z","timestamp":1745188536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Quantification of Methylene Blue and Evaluation of Its Pharmacokinetics in ICR Mice by Liquid Chromatography\u2010Quadrupole Time\u2010of\u2010Flight Mass Spectrometry Using Difluoroacetic Acid"],"prefix":"10.1002","volume":"39","author":[{"given":"Seo\u2010jin","family":"Park","sequence":"first","affiliation":[{"name":"Institute of Drug Research and Development, College of Pharmacy Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Drug Research and Development, College of Pharmacy Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangsoo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Institute of Drug Research and Development, College of Pharmacy Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong\u2010hyeon","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute of Drug Research and Development, College of Pharmacy Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjin","family":"Cho","sequence":"additional","affiliation":[{"name":"Institute of Drug Research and Development, College of Pharmacy Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7135-8988","authenticated-orcid":false,"given":"Young\u00a0G.","family":"Shin","sequence":"additional","affiliation":[{"name":"Institute of Drug Research and Development, College of Pharmacy Chungnam National University  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,20]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Akihiko Takashima B. 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