Simultaneous quantification of venetoclax, selinexor, voriconazole and fluconazole in human plasma by HPLC-MS/MS and its application in hematological malignancies

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.