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This study aims to validate a population pharmacokinetics model (popPK) for quizartinib in plasma samples of FLT3-ITD negative AML patients. To do so, an ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS\/MS) method has been developed and validated for the quantification of quizartinib.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Plasma samples were collected from FLT3-ITD negative newly diagnosed AML patients undergoing quizartinib therapy at induction in the QUIWI phase II clinical trial [NCT04107727, PETHEMA group] between March 2020 and February 2022. The UPLC-MS\/MS method was developed and validated. A previously described popPK model was validated using external validation techniques and implemented using the software NONMEM v7.5.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The developed UPLC-MS\/MS method demonstrated high accuracy and precision with a linear range of 6 to 200\u00a0ng\/mL, with relative standard deviation between 3\u201311 and accuracy of 88\u201397% from nominal values. The external validation of the quizartinib popPK model showed minimal bias at the population level (MdPE: -9.86%; ME: 0.50\u00a0ng\/mL, p\u2009=\u20090.964), but moderate imprecision (MdAPE: 32.28%) and suboptimal accuracy (F20: 24.5%; F30: 43.4%). Individual predictions improved performance, with negligible bias (MdPE: -0.50%), acceptable precision (MdAPE: 11.27%), and F20 (64.2%) and F30 (77.4%) exceeding predefined thresholds. Visual predictive checks confirmed adequate prediction of median concentrations, though some deviations occurred at extremes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study presents a replicable UPLC-MS\/MS method for the determination of quizartinib in plasma. The validated popPK model can be used to optimize dosing strategies in future clinical studies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00228-025-03909-4","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T05:38:19Z","timestamp":1756532299000},"page":"1699-1709","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Validation of pharmacokinetic model for quizartinib quantified by UPLC-MS\/MS in patients with FLT3-ITD negative newly diagnosed acute myeloid 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AbbVie: advisory board, speakers bureau, research support; Astellas: research support, consultant, speakers bureau, advisory board; Agios: consultant; Tolero Pharmaceutical: consultant; Glycomimetics: consultant; Forma Therapeutics: consultant; Celgene: research support, consultant, speakers bureau, advisory board; Daiichi Sankyo: research support, consultant, speakers bureau, advisory board; Incyte: speakers bureau, advisory board; Janssen: research support, speakers bureau, advisory board; Karyopharm: research support, advisory board; Novartis: research support, speakers bureau, advisory board; Pfizer: research support, speakers bureau, advisory board; Teva: research support, speakers bureau, advisory board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}