ArticleDrug design, development and therapy2025
Establishment and Validation of a UPLC-MS/MS Method for Quantitative Determination of Zanubrutinib and Posaconazole in Rat Plasma: Application in Drug-Drug Interaction Studies.
Article in Drug design, development and therapy, 2025. 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
Purpose: Zanubrutinib, a second-generation Bruton's tyrosine kinase (BTK) inhibitor, has been demonstrated to treat multiple B-cell malignancies, which include Waldenström's macroglobulinemia, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma and mantle cell lymphoma (MCL). There have been very few studies of drug-drug interactions (DDI) between zanubrutinib and other medications. Methods: The current study validated a sensitive and reliable quantitative detection of zanubrutinib and posaconazole in rat plasma using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The plasma samples were prepared by protein precipitation with the addition of acetonitrile, using orelabrutinib and fluconazole as internal standards (IS). Fifteen male Sprague-Dawley (SD) rats were randomly and equally divided into three groups: posaconazole (40 mg/kg) administered orally alone, zanubrutinib (16 mg/kg) received orally alone, co-administered orally zanubrutinib (16 mg/kg) and posaconazole (40 mg/kg). Results: The methodology was validated, and the precision, stability, accuracy, matrix effect and extraction recovery were within the permissible values. This method was successfully applied to evaluate the potential DDI between zanubrutinib and posaconazole, and the results showed a significant 0.98-fold increase in both AUC Conclusion: These data suggested that when zanubrutinib was co-administered with posaconazole, there are increased exposures to both zanubrutinib and posaconazole. The current results contributed to a better understanding of the metabolism and DDI of zanubrutinib and posaconazole, and it is necessary to further investigate and validate the results in humans.
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