{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:12:44Z","timestamp":1789114364457,"version":"build-2803163510"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Venetoclax and selinexor are essential targeted agents for hematological malignancies, but their clinical application is challenged by pronounced ethnic pharmacokinetic differences\u2014especially in Chinese patients\u2014and CYP3A-mediated drug-drug interactions (DDIs) with azole antifungals (voriconazole, fluconazole). No existing LC-MS\/MS method simultaneously quantifies all four drugs, creating an unmet need for therapeutic drug monitoring (TDM). We aimed to develop and validate a rapid, sensitive HPLC-MS\/MS method for simultaneous quantification of venetoclax, selinexor, voriconazole, and fluconazole in human plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma samples underwent protein precipitation pretreatment. Chromatographic separation utilized a C18 column with acetonitrile and 0.1% formic acid gradient elution. Mass detection employed positive-ion multiple reaction monitoring (MRM). The method was validated for specificity, linearity, precision, accuracy, recovery, matrix effect, and stability, then applied to AML patients receiving these medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Calibration ranges were 40\u20138000\u00a0ng\/mL (venetoclax), 5\u20131000\u00a0ng\/mL (selinexor), 100\u201310000\u00a0ng\/mL (voriconazole), and 320\u201332000\u00a0ng\/mL (fluconazole), all with\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      &amp;gt; 0.9976. Intra-day and inter-day precision and accuracy met acceptance criteria. No significant matrix effect or carry-over was observed. Selinexor exhibited limited stability (&amp;lt;85% remaining after 4\u00a0h at room temperature or 24\u00a0h at 4\u00a0\u00b0C); other analytes were stable throughout. The median venetoclax steady-state trough concentration (Css,trough) in Chinese patients was 1025.08\u00a0ng\/mL. Co-administration with voriconazole increased venetoclax exposure 1.75\u201314-fold, whereas fluconazole produced a consistent 2.4\u20132.9-fold increase. Venetoclax 100\u00a0mg\/d combined with azole antifungals achieved exposures comparable to or exceeding 400\u00a0mg\/d monotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first HPLC-MS\/MS method enabling simultaneous quantification of venetoclax, selinexor, voriconazole, and fluconazole, successfully deployed in routine TDM. Voriconazole\u2019s marked DDI variability underscores the necessity of TDM-guided dosing, while fluconazole offers a more predictable antifungal prophylaxis alternative. These results deliver population-specific pharmacokinetic data supporting rational co-administration of venetoclax with azole antifungals in Chinese hematologic malignancy patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1827916","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:18:43Z","timestamp":1789111123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Simultaneous quantification of venetoclax, selinexor, voriconazole and fluconazole in human plasma by HPLC-MS\/MS and its application in hematological malignancies"],"prefix":"10.3389","volume":"17","author":[{"given":"Feifei","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Institute for Cancer, Chinese Institutes for Medical Research (CIMR)","place":["Beijing, China"]},{"name":"Beijing Key Laboratory of Tumour Resistance Mechanism and Clinical Translation","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoling","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","year":"2018"},{"key":"B2","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa1903455","article-title":"Oral selinexor-dexamethasone for triple-class refractory multiple myeloma","volume":"381","author":"Chari","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.3390\/pharmaceutics15061680","article-title":"Pharmacokinetics of venetoclax Co-Administered with posaconazole in patients with acute myeloid leukemia","volume":"15","author":"De Gregori","year":"2023","journal-title":"Pharmaceutics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1056\/NEJMoa2213093","article-title":"First-line venetoclax combinations in chronic lymphocytic leukemia","volume":"388","author":"Eichhorst","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"115279","DOI":"10.1016\/j.jpba.2023.115279","article-title":"Simultaneous quantification of venetoclax and voriconazole in human plasma by UHPLC-MS\/MS and its application in acute myeloid leukemia patients","volume":"227","author":"Gao","year":"2023","journal-title":"J. Pharm. Biomed. 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Natl. Compr. Canc Netw."},{"key":"B12","doi-asserted-by":"publisher","first-page":"772","DOI":"10.3760\/cma.j.cn121090-20231031-00241","article-title":"The clinical safety and efficacy of selinexor combined with venetoclax and azactitidine induction therapy in relapsed and refractory acute myeloid leukemia","volume":"45","author":"Liu","year":"2024","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"B13","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41698-022-00315-2","article-title":"Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14)","volume":"6","author":"Nguyen","year":"2022","journal-title":"NPJ Precis. Oncol."},{"key":"B14","year":"2020"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1002\/cncr.33508","article-title":"Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia","volume":"127","author":"Rausch","year":"2021","journal-title":"Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1007\/s40265-019-01188-9","article-title":"Selinexor: first global approval","volume":"79","author":"Syed","year":"2019","journal-title":"Drugs"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1477697","DOI":"10.3389\/fonc.2024.1477697","article-title":"Selinexor in combination with venetoclax and decitabine in patients with refractory myelodysplastic syndrome previously exposed to hypomethylating agents: three case reports","volume":"14","author":"Xiao","year":"2024","journal-title":"Front. Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e70006","DOI":"10.1111\/cts.70006","article-title":"Paired comparisons of venetoclax concentration in cerebrospinal fluid, bone marrow, and plasma in acute leukemia patients","volume":"17","author":"Yuan","year":"2024","journal-title":"Clin. Transl. Sci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1827916\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:18:44Z","timestamp":1789111124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1827916\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":18,"alternative-id":["10.3389\/fphar.2026.1827916"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1827916","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1827916"}}