{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:29:15Z","timestamp":1786616955372,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82173958"],"award-info":[{"award-number":["No. 82173958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. U24A20793"],"award-info":[{"award-number":["No. U24A20793"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["No. 24ZR1467100"],"award-info":[{"award-number":["No. 24ZR1467100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010876","name":"Shanghai University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["21DZ2270500"],"award-info":[{"award-number":["21DZ2270500"]}],"id":[{"id":"10.13039\/501100010876","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mailuoning oral liquid (MLN) is a state\u2010approved multi\u2010herb formula that has been prescribed for 25 years to clear heat, nourish yin, invigorate blood, and resolve stasis. Although randomized controlled trials and real\u2010world evidence support its efficacy in thromboangiitis obliterans, deep\u2010vein thrombosis, and the convalescent phase of cerebral infarction, a systematic search\u00a0identified no pharmacokinetic data on its bioactive constituents. This lack of pharmacokinetic data impedes evidence\u2010based dose refinement and international acceptance. Here, we employed ultra\u2010high\u2010performance liquid chromatography with Quadrupole\u2010Exactive Orbitrap high\u2010resolution mass spectrometry (UHPLC\u2010Q\u2010Exactive Orbitrap HRMS) to track 39 MLN\u2010derived compounds in rat plasma, intestinal contents, and 10 tissues; 15 with prominent systemic exposure were designated as key pharmacokinetic markers. A selective and sensitive UHPLC\u2010tandem MS assay was subsequently developed and fully validated for simultaneous quantification of these 15 circulating components. The assay exhibited excellent linearity (\n                    <jats:italic>r<\/jats:italic>\n                    \u2265 0.9974) for all analytes, with precision, accuracy, extraction recovery, and matrix effects meeting standard bioanalytical validation criteria. All compounds demonstrated stability under the tested storage conditions. Following oral administration of MLN at 8.1 and 16.2 mL\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    in rats, all 15 components were rapidly absorbed, reaching peak plasma concentrations within approximately 1 h. Systemic exposure increased in a clear dose\u2010dependent manner, with structurally related compounds showing similar pharmacokinetic profiles. Notably, the iridoids secoxyloganin, harpagide, and secologanic acid yielded the highest AUC\n                    <jats:sub>0<\/jats:sub>\n                    \u2013\n                    <jats:sub>24\u00a0h<\/jats:sub>\n                    values, indicating they are the principal systemic exposure markers. This study establishes the first comprehensive pharmacokinetic profile for MLN and provides a robust, validated analytical platform. By creating a crucial link between quantitative systemic exposure and efficacy, our work supplies a scientific foundation for refining dosage regimens, establishing quality specifications, and promoting the evidence\u2010based clinical application of this widely prescribed traditional Chinese medicine formula.\n                  <\/jats:p>","DOI":"10.1002\/jssc.70481","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:58:53Z","timestamp":1783688333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Exposure and Multicomponent Pharmacokinetics of Mailuoning Oral Liquid: Integrated Ultra\u2010High\u2010Performance Liquid Chromatography\u2010High\u2010Resolution Mass Spectrometry Profiling and Ultra\u2010High\u2010Performance Liquid Chromatography\u2010Tandem Mass Spectrometry Quantification"],"prefix":"10.1002","volume":"49","author":[{"given":"Sijia","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"},{"name":"Department of Pharmacy, The NATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangya","family":"Jia","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiekai","family":"Hua","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"},{"name":"School of Pharmacy Hangzhou Normal University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jian","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The NATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhen","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics China Pharmaceutical University  Nanjing China"},{"name":"Technology Center of Jinling Pharmaceutical Co., Ltd.  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The NATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica Shanghai University of Traditional Chinese 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