Publication Date
11-1-2022
Journal
Journal of Mass Spectrometry and Advances in the Clinical Lab
DOI
10.1016/j.jmsacl.2022.09.004
PMID
36388060
PMCID
PMC9641598
PubMedCentral® Posted Date
9-14-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Atovaquone, Therapeutic drug monitoring, Acute myeloid leukemia, LC-MS/MS
Abstract
BACKGROUND: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.
METHODS: Atovaquone was extracted from a 10 µL volume of K
RESULTS: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min per injection, and retention times of 4.3 min. Atovaquone was measured over a dynamic concentration range of 0.63 - 80 µM with a deviation within ≤ ± 5.1 % of the target value. Intra- and inter-assay precision were ≤ 2.7 % and ≤ 8.4 %, respectively. Dilutional, carryover, and interference studies were also within acceptable limits.
CONCLUSIONS: Our studies have shown that our LC-MS/MS-based method is both reliable and robust for the quantification of plasma atovaquone concentrations and can be used to determine the effective dose of atovaquone for pediatric patients treated for AML.
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