{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:26:38Z","timestamp":1786692398869,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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":["82404747"],"award-info":[{"award-number":["82404747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cyclophosphamide (CP) is a common alkylating anticancer drug. Artemisinin (ART), an antimalarial agent metabolized by hepatic CYP450s, exhibits promising antitumor activity. This study established a rapid and accurate LC\u2010MS\/MS method for the quantitative analysis of CP and its metabolite in mouse plasma, as well as to apply this method in assessing how ART influences the pharmacokinetics of CP. Given the instability of 4\u2010OH\u2010CP, 4\u2010keto\u2010CP was selected as a surrogate metabolite for detection. The effect of ART on the mRNA expression and activity of CYP450 enzymes were assessed by RT\u2010qPCR and substrate cocktail assay. The results indicated that CP and 4\u2010keto\u2010CP were linear in the range of 1\u20132000 and 2\u20132000\u2009ng\/mL, respectively. The accuracy, precision, extraction recovery, stability, and matrix effect of CP and 4\u2010keto\u2010CP are complied with the Bioanalytical Method Validation Guidelines. ART significantly reduced the\n                    <jats:italic>AUC<\/jats:italic>\n                    <jats:sub>\n                      0\u2212\n                      <jats:italic>t<\/jats:italic>\n                    <\/jats:sub>\n                    of CP by 26.6%, while increasing CL\/F by 1.35\u2010fold. Concurrently, the\n                    <jats:italic>AUC<\/jats:italic>\n                    <jats:sub>\n                      0\u2212\n                      <jats:italic>t<\/jats:italic>\n                    <\/jats:sub>\n                    and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>max<\/jats:italic>\n                    <\/jats:sub>\n                    of 4\u2010keto\u2010CP increased by 1.42\u2010 and 1.45\u2010fold, respectively. Furthermore, ART can markedly upregulate the mRNA expression and activity of CAR\/\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    . The results showed that pretreatment with ART could induce CP metabolism to its active metabolite. This study provides implications for the rational use of the ART\u2010CP combination in clinical practice.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70589","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T06:25:42Z","timestamp":1786083942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Artemisinin on the Pharmacokinetics of Cyclophosphamide and Its Metabolite in Mice and Its Potential Mechanisms"],"prefix":"10.1002","volume":"40","author":[{"given":"Huilong","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Wannan Medical University  Wuhu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Wannan Medical University  Wuhu 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