Determination of 5-azacitidine in human plasma by LC–MS/MS: application to pharmacokinetics pilot study in MDS/AML patients.

Autor: Donnette, Melanie, Osanno, Loic, Giocanti, Madeleine, Venton, Geoffroy, Farnault, Laure, Berda-Haddad, Yael, Costello, Régis, Caroline, Solas, Ouafik, L.'Houcine, Ciccolini, Joseph, Fanciullino, Raphaëlle
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Zdroj: Cancer Chemotherapy & Pharmacology; Mar2023, Vol. 91 Issue 3, p231-238, 8p
Abstrakt: Purpose: Azacitidine (Vidaza®, AZA) is a mainstay for treating acute myeloid leukemia (AML) in patients unfit for standard induction and other myelodysplastic syndromes (MDS). However, only half of the patients usually respond to this drug and almost all patients will eventually relapse. Predictive markers for response to AZA are yet to be identified. AZA is metabolized in the liver by a single enzyme, cytidine deaminase (CDA). CDA is a ubiquitous enzyme coded by a highly polymorphic gene, with subsequent great variability in resulting activities in the liver. The quantitative determination of AZA in plasma is challenging due the required sensitivity and because of the instability in the biological matrix upon sampling, possibly resulting in erratic values. Methods: We have developed and validated following EMA standards a simple, rapid, and cost-effective liquid chromatography–tandem mass spectrometry method for the determination of azacitidine in human plasma. Results: After a simple and rapid precipitation step, analytes were successfully separated and quantitated over a 5–500 ng/mL range. The performance and reliability of this method were tested as part of an investigational study in MDS/AML patients treated with standard azacitidine (75 mg/m2 for 7 days a week every 28 days). Conclusion: Overall, this new method meets the requirements of current bioanalytical guidelines and could be used to monitor drug levels in MDS/AML patients. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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