{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:24:54Z","timestamp":1786973094842,"version":"build-2736575974"},"reference-count":36,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":", Thailand Research Fund","doi-asserted-by":"publisher","award":["DBG"],"award-info":[{"award-number":["DBG"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A liquid chromatography-tandem mass spectrometry (LC-MS\/MS) method was developed and validated to determine hexahydrocurcumin (HHC) levels in mouse plasma, brain, liver, and kidneys using a negative ion mode electrospray ionization (ESI) source. Demonstrating a lower limit of quantification (LLOQ) of 5 ng\/mL, the method showed excellent linearity across a concentration range of 5\u2013500 ng\/mL in all tested matrices. Precision evaluations reported a coefficient of variation (CV%) of less than 13.19% for both intraday and interday measurements, while accuracy ranged from 95.13 to 105.07% across all quality control levels. HHC extraction recovery was consistently observed between 70.18 and 93.28%, with a CV% deviation of less than 15%. In the pharmacokinetic evaluation of HHC in mice following a single intraperitoneal (IP) or oral administration, a noncompartment analysis was utilized. After IP administration (40 mg\/kg), the Cmax value was 47.90 times higher than that achieved via oral administration. Peak plasma concentrations were observed approximately 5 min post-IP and 15 min post-oral dosing. The observed half-lives after these administrations were approximately 1.52 and 2.17 h for IP and oral routes, respectively. Oral administration revealed a relative bioavailability of only 12.28% compared with the IP route. Furthermore, following IP administration, the half-life values in brain, liver, and kidney were not significantly different but more than the half-life value found in plasma. The liver and kidney exhibited the highest concentrations of HHC, while the brain showed the least, suggesting that the hydrophobic nature of HHC impedes its passage through the blood\u2013brain barrier. This study is the first to provide detailed insights into the pharmacokinetics and tissue distribution characteristics of HHC following oral and IP administration in mice, setting the stage for further focus on HHC as a potential new drug candidate.<\/jats:p>","DOI":"10.1021\/acsomega.4c06604","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T12:29:09Z","timestamp":1726748949000},"page":"41032-41042","source":"Crossref","is-referenced-by-count":8,"title":["Comparative Pharmacokinetics\nand Tissue Distribution\nof Hexahydrocurcumin Following Intraperitoneal vs Oral Administration\nin Mice Using LC-MS\/MS"],"prefix":"10.1021","volume":"9","author":[{"given":"Worawut","family":"Chaiyasaeng","sequence":"first","affiliation":[{"name":"Ramkhamhaeng University , , Bangkapi, ,","place":["Bangkok, Thailand, 10240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7043-2867","authenticated-orcid":true,"given":"Darunee","family":"Hongwiset","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , ,","place":["Chiang\nMai, Thailand, 50200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chainarong","family":"Tocharus","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , ,","place":["Chiang Mai, Thailand, 50200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baralee","family":"Punyawudho","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , ,","place":["Chiang\nMai, Thailand, 50200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiraporn","family":"Tocharus","sequence":"additional","affiliation":[{"name":"Chiang Mai University , , ,","place":["Chiang Mai, Thailand, 50200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waraluck","family":"Chaichompoo","sequence":"additional","affiliation":[{"name":"Ramkhamhaeng University , , Bangkapi, ,","place":["Bangkok, Thailand, 10240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1391-6993","authenticated-orcid":true,"given":"Pornchai","family":"Rojsitthisak","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]},{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6445-7550","authenticated-orcid":true,"given":"Wachirachai","family":"Pabuprapap","sequence":"additional","affiliation":[{"name":"Ramkhamhaeng University , , Bangkapi, ,","place":["Bangkok, Thailand, 10240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9513-7282","authenticated-orcid":true,"given":"Boon-ek","family":"Yingyongnarongkul","sequence":"additional","affiliation":[{"name":"Ramkhamhaeng University , , Bangkapi, ,","place":["Bangkok, Thailand, 10240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8919-3555","authenticated-orcid":true,"given":"Apichart","family":"Suksamrarn","sequence":"additional","affiliation":[{"name":"Ramkhamhaeng University , , Bangkapi, ,","place":["Bangkok, Thailand, 10240"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"issue":"11","key":"2026081708293244500_cit1","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1016\/j.bcp.2008.08.008","article-title":"Biological activities of curcumin\nand its analogues (Congeners) made by man and Mother Nature","volume":"76","author":"Anand","year":"2008","journal-title":"Biochem. 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Gastroenterol."},{"issue":"11","key":"2026081708293244500_cit16","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1002\/ptr.5448","article-title":"Mechanisms of vasorelaxation induced\nby hexahydrocurcuminin isolated rat thoracic aorta","volume":"29","author":"Moohammadaree","year":"2015","journal-title":"Phytother. Res."},{"issue":"3","key":"2026081708293244500_cit17","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s43440-019-00050-9","article-title":"Hexahydrocurcumin alleviated blood-brain\nbarrier dysfunction in cerebral ischemia\/reperfusion\nrats","volume":"72","author":"Wicha","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"2026081708293244500_cit18","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1007\/s12640-020-00269-y","article-title":"Inhibitory effect of hexahydrocurcumin\non memory impairment and amyloidogenesis in dexamethasone-treated mice","volume":"39","author":"Jearjaroen","year":"2021","journal-title":"Neurotoxic. 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Dispos."},{"issue":"3","key":"2026081708293244500_cit28","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1021\/jf803038f","article-title":"Rapid analysis of curcumin and curcumin\nmetabolites in rat biomatrices using a novel ultraperformance liquid\nchromatography (UPLC) method","volume":"57","author":"Marczylo","year":"2009","journal-title":"J. Agric. Food\nChem."},{"issue":"9","key":"2026081708293244500_cit29","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.4267","article-title":"The pharmacokinetics\nand tissue distribution of curcumin and its metabolites in mice","volume":"32","author":"Wang","year":"2018","journal-title":"Biomed. Chromatogr."},{"issue":"1","key":"2026081708293244500_cit30","doi-asserted-by":"publisher","DOI":"10.1186\/2008-2231-21-11","article-title":"Development\nof a validated UPLC-qTOF-MS method for the determination of curcuminoids\nand their pharmacokinetic study in mice","volume":"21","author":"Verma","year":"2013","journal-title":"Daru,\nJ. Pharm. Sci."},{"issue":"1","key":"2026081708293244500_cit31","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-019-2745-x","article-title":"Intraperitoneal\nRoute of Drug Administration: Should it Be Used in Experimental Animal\nStudies?","volume":"37","author":"Al\nShoyaib","year":"2020","journal-title":"Pharm. Res."},{"issue":"1","key":"2026081708293244500_cit32","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.ijpharm.2016.07.027","article-title":"Bioavailability\nof curcumin and curcumin glucuronide in the central nervous system\nof mice after oral delivery of nano-curcumin","volume":"511","author":"Szymusiak","year":"2016","journal-title":"Int. J. Pharm."},{"key":"2026081708293244500_cit33","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3390\/ph17020164","article-title":"Bioavailability of Oral Curcumin\nin Systematic Reviews: A Methodological Study","volume":"17","author":"Buc\u030cevic\u0301\nPopovic\u0301","year":"2024","journal-title":"Pharmaceuticals"},{"key":"2026081708293244500_cit34","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/678218","article-title":"Curcumin\nPharmacokinetic and Pharmacodynamic\nEvidences in Streptozotocin-Diabetic Rats Support the Antidiabetic\nActivity to Be via Metabolite(s)","volume":"2015","author":"Gutierres","year":"2015","journal-title":"J. Evidence-Based\nComplementary Altern. 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