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CAM106, a rupestonic acid derivative, was studied for its potent antiviral activity and showed a favorable inhibitory effect on influenza virus replication. However, many gaps exist in preclinical studies of CAM106. This study focused on the pharmacokinetic profile and metabolites of CAM106 in vivo. An efficient and fast bioanalytical method was successfully developed and validated for the quantitation of CAM106 in rat plasma. A mobile phase aqueous solution (A, containing 0.1% formic acid) and acetonitrile (B) worked within 0\u20133.5 min, with 60% B. The mass spectrum scanning mode was the parallel reaction monitoring (PRM) with a resolution of 17,500. The linear range of the method was 2.13\u20131063.83 ng\/mL. The validated method was applied to a pharmacokinetic study in rats. The matrix effects ranged from 93.99% to 100.08% and the recovery ranged from 86.72% to 92.87%. The intra- and inter-day precisions were less than 10.24% and the relative error (RE) ranged from \u22128.92% to 7.1%. The oral bioavailability of CAM106 was 1.6%. Thereafter, its metabolites in rats were characterized using high-resolution mass spectrometry. The isomers M7-A, M7-B, M7-C, and M7-D were well separated. As a result, a total of 11 metabolites were identified in the feces, urine, and plasma of rats. The main metabolic pathways of CAM106 were oxidation, reduction, desaturation, and methylation. The assay was reliable and provided useful information for further clinical studies of CAM106.<\/jats:p>","DOI":"10.3390\/ph16050728","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T03:22:19Z","timestamp":1683775339000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetic Study and Metabolite Identification of CAM106 in Rats by Validated UHPLC-MS\/MS"],"prefix":"10.3390","volume":"16","author":[{"given":"Ruqi","family":"Xi","sequence":"first","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"},{"name":"University of Chinese Academy of Sciences, No. 19(A) Yuquan Road, Shijingshan District, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahima","family":"Abdulla","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4652-6879","authenticated-orcid":false,"given":"Haji Akber","family":"Aisa","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2144-4474","authenticated-orcid":false,"given":"Yongqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00061-19","DOI":"10.1128\/MMBR.00061-19","article-title":"Global organization and proposed megataxonomy of the virus world","volume":"84","author":"Koonin","year":"2020","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41591-020-0843-2","article-title":"Respiratory virus shedding in exhaled breath and efficacy of face masks","volume":"26","author":"Leung","year":"2020","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1097\/QCO.0000000000000563","article-title":"Controversy around airborne versus droplet transmission of respiratory viruses: Implication for infection prevention","volume":"32","author":"Shiu","year":"2019","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.chom.2022.06.008","article-title":"The logic of virus evolution","volume":"30","author":"Koonin","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/j.cell.2020.10.019","article-title":"Translation and replication dynamics of single RNA viruses","volume":"183","author":"Boersma","year":"2020","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.cois.2021.12.003","article-title":"Bracoviruses, ichnoviruses, and virus-like particles from parasitoid wasps retain many features of their virus ancestors","volume":"49","author":"Drezen","year":"2022","journal-title":"Curr. Opin. Insect Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virol.2022.03.014","article-title":"Modulation of Zika virus replication via glycosphingolipids","volume":"572","author":"Konan","year":"2022","journal-title":"Virology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"04028","DOI":"10.7189\/jogh.12.04028","article-title":"Health disparity and mortality trends of infectious diseases in BRICS from 1990 to 2019","volume":"12","author":"Liu","year":"2022","journal-title":"J. Glob. Health"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maleski, A.L.A., Rosa, J.G.S., Bernardo, J.T.G., Astray, R.M., Walker, C.I.B., Lopes-Ferreira, M., and Lima, C. (2022). Recapitulation of retinal damage in zebrafish larvae infected with Zika Virus. Cells, 11.","DOI":"10.3390\/cells11091457"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1038\/s41467-022-32234-y","article-title":"Zika vector competence data reveals risks of outbreaks: The contribution of the European ZIKAlliance project","volume":"13","author":"Obadia","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/bs.enz.2021.09.002","article-title":"Structure and function of negative-strand RNA virus polymerase complexes","volume":"50","author":"Pyle","year":"2021","journal-title":"Enzymes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.virol.2019.05.008","article-title":"Two novel fungal negative-strand RNA viruses related to mymonaviruses and phenuiviruses in the shiitake mushroom (Lentinula edodes)","volume":"533","author":"Lin","year":"2019","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/zph.12685","article-title":"Human-infecting influenza A (H9N2) virus: A forgotten potential pandemic strain?","volume":"67","author":"Song","year":"2020","journal-title":"Zoonoses Public Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S0140-6736(22)00982-5","article-title":"Influenza","volume":"400","author":"Uyeki","year":"2022","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.3201\/eid1211.060426","article-title":"Review of aerosol transmission of influenza A virus","volume":"12","author":"Tellier","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.3201\/eid2812.221086","article-title":"Iceland as stepping stone for spread of highly pathogenic avian influenza virus between Europe and North America","volume":"28","author":"Gunther","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1126\/science.296.5566.211a","article-title":"Questioning the evidence for genetic recombination in the 1918 \u201cSpanish flu\u201d virus\u2014Response","volume":"296","author":"Gibbs","year":"2002","journal-title":"Science"},{"key":"ref_18","first-page":"1704","article-title":"The influenza epidemic of 1957\u201358 in Sweden; epidemiology","volume":"60","author":"Korlof","year":"1958","journal-title":"Nord. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"John Wiley & Sons, Inc (1968). Influenza: The virus Hong Kong virus. Med. J. Aust., 2, 196.","DOI":"10.5694\/j.1326-5377.1968.tb83320.x"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1128\/JCM.02464-09","article-title":"Evaluation of Three Influenza A and B Real-Time Reverse Transcription-PCR Assays and a New 2009 H1N1 Assay for Detection of Influenza Viruses","volume":"48","author":"Selvaraju","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molimm.2021.05.012","article-title":"Inhibition of histone deacetylase 1 suppresses pseudorabies virus infection through cGAS-STING antiviral innate immunity","volume":"136","author":"Guo","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s42764-022-00064-3","article-title":"Single-stranded RNA viruses activate and hijack host apical DNA damage response kinases for efficient viral replication","volume":"3","author":"Li","year":"2022","journal-title":"Genome Instab. Dis."},{"key":"ref_23","first-page":"310","article-title":"Advances in studies on the rupestonic acid derivatives as anti-influenza agents","volume":"13","author":"Yong","year":"2013","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.6023\/cjoc1108081","article-title":"Synthesis of Novel Isoxazole Contained Rupestonic Acid Derivatives and In Vitro Inhibitory Activity against Influenza Viruses A and B","volume":"32","author":"Zhao","year":"2012","journal-title":"Chin. J. Org. Chem."},{"key":"ref_25","first-page":"4565","article-title":"Chemical constituents, biological activities and clinical applications of artemisia rupestris","volume":"42","author":"Wan","year":"2017","journal-title":"Chin. J. Chin. Mater. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s10600-017-2181-2","article-title":"Chemical constituents of artemisia rupestris","volume":"53","author":"Wu","year":"2017","journal-title":"Chem. Nat. Compd."},{"key":"ref_27","first-page":"363","article-title":"Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b)","volume":"14","author":"Yu","year":"2016","journal-title":"Chin. J. Nat. Med."},{"key":"ref_28","first-page":"1672","article-title":"Simultaneous determination of 5 constituents in Artemisia rupestris L. by HPLC-MS\/MS","volume":"33","author":"Cai","year":"2013","journal-title":"Chin. J. Pharm. Anal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.freeradbiomed.2016.04.021","article-title":"Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response","volume":"96","author":"Ma","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e5488","DOI":"10.1002\/bmc.5488","article-title":"Simultaneous determination and pharmacokinetic study of six components in beagle dog plasma by UPLC-MS\/MS after oral administration of Astragalus Membranaceus aqueous extract","volume":"36","author":"Yu","year":"2022","journal-title":"Biomed. Chromatogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102178","DOI":"10.1016\/j.jddst.2020.102178","article-title":"A comprehensive review of the strategies to improve oral drug absorption with special emphasis on the cellular and molecular mechanisms","volume":"61","author":"Padhye","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_32","unstructured":"(2023, March 29). Bioanalytical Method Validation Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/bioanalytical-method-validation-guidance-industry."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:32:36Z","timestamp":1760124756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,11]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ph16050728"],"URL":"https:\/\/doi.org\/10.3390\/ph16050728","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,11]]}}}