ArticleFrontiers in pharmacology2026
Simultaneous quantification of venetoclax, selinexor, voriconazole and fluconazole in human plasma by HPLC-MS/MS and its application in hematological malignancies.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Venetoclax and selinexor are essential targeted agents for hematological malignancies, but their clinical application is challenged by pronounced ethnic pharmacokinetic differences-especially in Chinese patients-and 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. Methods: 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. Results: Calibration ranges were 40-8000 ng/mL (venetoclax), 5-1000 ng/mL (selinexor), 100-10000 ng/mL (voriconazole), and 320-32000 ng/mL (fluconazole), all with Conclusion: This is the first HPLC-MS/MS method enabling simultaneous quantification of venetoclax, selinexor, voriconazole, and fluconazole, successfully deployed in routine TDM. Voriconazole's 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.
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