{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:55:43Z","timestamp":1768434943270,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alizarin (1,2\u2010dihydroxyanthraquinone) is an anthraquinone reddish dye widely used for painting and textile dyeing. As the biological activity of alizarin has recently attracted increasing attention from researchers, its therapeutic potential as complementary and alternative medicine is of interest. However, no systematic research has been conducted on the biopharmaceutical and pharmacokinetic aspects of alizarin. Therefore, this study aimed to comprehensively investigate the oral absorption and intestinal\/hepatic metabolism of alizarin using a simple and sensitive tandem mass spectrometry method developed and validated in\u2010house. The present method for the bioanalysis of alizarin has merits, including a simple pretreatment procedure, small sample volume, and adequate sensitivity. Alizarin exhibited pH\u2010dependent moderate lipophilicity and low solubility with limited intestinal luminal stability. Based on the in vivo pharmacokinetic data, the hepatic extraction ratio of alizarin was estimated to be 0.165\u20130.264, classified as a low level of hepatic extraction. In an in situ loop study, considerable fractions (28.2%\u201356.4%) of the alizarin dose were significantly absorbed in gut segments from the duodenum to ileum, suggesting that alizarin may be classified as the Biopharmaceutical Classification System\u00a0class II. An in vitro metabolism study using rat and human hepatic S9 fractions revealed that glucuronidation and sulfation, but not NADPH\u2010mediated phase I reactions and methylation, are significantly involved in the hepatic metabolism of alizarin. Taken together, it can be estimated that the fractions of oral alizarin dose unabsorbed from the gut lumen and eliminated by the gut and liver before reaching the systemic circulation are 43.6%\u201376.7%, 0.474%\u201336.3%, and 3.77%\u20135.31% of the dose, respectively, resulting in a low oral bioavailability of 16.8%. Therefore, the oral bioavailability of alizarin depends primarily on its chemical degradation in the gut lumen and secondarily on first\u2010pass metabolism.<\/jats:p>","DOI":"10.1002\/ddr.22047","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T10:53:05Z","timestamp":1677063185000},"page":"569-581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC\u2010MS\/MS method: In vitro, in situ, and in vivo evaluations"],"prefix":"10.1002","volume":"84","author":[{"given":"Seong\u2010Wook","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development Pusan National University  Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Gyun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development Pusan National University  Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Mee","family":"Baek","sequence":"additional","affiliation":[{"name":"Cultural Heritage Preservation Research Institute Pusan National University  Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Chul","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research Inje University  Gimhae South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Wook","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development Pusan National University  Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunjin","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development Pusan National University  Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han\u2010Joo","family":"Maeng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Gachon University  Incheon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heejoon","family":"Myung","sequence":"additional","affiliation":[{"name":"LyseNTech Co., Ltd.  Seongnam\u2010si Gyunggi South Korea"},{"name":"Department of Bioscience and Biotechnology Hankuk University of Foreign Studies  Yongin\u2010si Gyunggi South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-5723","authenticated-orcid":false,"given":"In\u2010Soo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development Pusan National University  Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/scipharm88040051"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scijus.2020.11.006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2022.123399"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.03.173"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201700981"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24112180"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13020175"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0AY00471E"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11080382"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113141"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2019.05.023"},{"key":"e_1_2_10_13_1","first-page":"432","article-title":"Alizarin as an indicator of bone growth","volume":"94","author":"Hoyte D. A.","year":"1960","journal-title":"Journal of Anatomy"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2009.10.019"},{"issue":"12","key":"e_1_2_10_15_1","first-page":"637","article-title":"Pharmacokinetic studies of alizarin in man","volume":"7","author":"Lorenz D.","year":"1985","journal-title":"Methods and Findings in Experimental and Clinical Pharmacology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00447"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2009.05.044"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112520"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2020.122508"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11120673"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.04.007"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(02)00212-9"},{"key":"e_1_2_10_23_1","unstructured":"USA Food and Drug Administration(2018).Bioanalytical method validation. US FDA.\u00a0https:\/\/www.fda.gov\/media\/70858\/download"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dyepig.2007.01.015"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2018-0515"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.70567"},{"issue":"5","key":"e_1_2_10_27_1","first-page":"1032","article-title":"The utility of alizarin red s staining in calcium pyrophosphate dihydrate crystal deposition disease","volume":"30","author":"Yamakawa K.","year":"2003","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327115595687"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.22047","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.22047","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.22047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T21:36:13Z","timestamp":1760391373000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.22047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,22]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/ddr.22047"],"URL":"https:\/\/doi.org\/10.1002\/ddr.22047","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,22]]},"assertion":[{"value":"2022-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}