Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients

• DOI: 10.1016/j.jmsacl.2022.09.004
• Publication Date: 2022-09-14T11:37:57Z
• Authors: Thomas D. Horvath; Izmarie Poventud-...; Lily Olayinka; Asha James; Sigmund J. Haidacher; Kathleen M. Hoch; Alexandra M. Stevens; Anthony M. Haag; Sridevi Devaraj
• Keywords: Therapeutic Drug Monitoring; Atovaquone

Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially pediatric patients. goal of our study was to develop validate performance assay quantify plasma concentrations collected from cancer patients using LC-MS/MS. extracted a 10 µL volume K2-EDTA human solution consisting ACN: EtOH: DMF (8:1:1 v:v:v), separated reverse-phase chromatography, detected SCIEX 5500 QTrap MS system. LC-MS/MS evaluated precision, accuracy, carryover, sensitivity, specificity, linearity, interferences. deuterated internal standard were analyzed gradient chromatographic method that had overall cycle-time 7.4 min per injection, retention times 4.3 min. measured over dynamic concentration range 0.63 - 80 µM with deviation within ≤ ± 5.1 % target value. Intra- inter-assay precision 2.7 8.4 %, respectively. Dilutional, interference also acceptable limits. Our LC-MS/MS-based is both reliable robust quantification can be determine effective dose treated AML.