未经批准:阿托瓦喹传统上被用作抗寄生虫和抗真菌药,但是最近的研究显示了它作为抗癌药物的潜力。atovaquone生物利用度的高变异性突出了治疗药物监测的需要,尤其是儿科患者。我们研究的目的是开发和验证使用LC-MS/MS定量从儿科癌症患者收集的atovaquone血浆浓度的测定法的性能。
UNASSIGNED:使用由ACN:EtOH:DMF(8:1:1v:v:v)组成的溶液从10μL体积的K2-EDTA人血浆中提取Atovaquone,使用反相色谱分离,并使用SCIEX5500QTrapMS系统进行检测。LC-MS/MS测定性能进行了精密度评估,准确度,结转,灵敏度,特异性,线性度和干扰。
UNASSIGNED:使用梯度色谱法分析了Atovaquone及其氘代内标,该方法每次注射的总循环时间为7.4分钟,保留时间为4.3min。在0.63-80µM的动态浓度范围内测量了Atovaquone,其偏差在目标值的≤±5.1%范围内。试验内和试验间精密度≤2.7%和≤8.4%,分别。稀释,结转,干扰研究也在可接受的范围内。
UNASSIGNED:我们的研究表明,我们的基于LC-MS/MS的方法对于定量血浆阿托伐酮浓度既可靠又稳健,可用于确定阿托伐酮的有效剂量用于治疗AML的儿科患者。
UNASSIGNED: 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.
UNASSIGNED: Atovaquone was extracted from a 10 µL volume of K2-EDTA human plasma using a solution consisting of ACN: EtOH: DMF (8:1:1 v:v:v), separated using reverse-phase chromatography, and detected using a SCIEX 5500 QTrap MS system. LC-MS/MS assay performance was evaluated for precision, accuracy, carryover, sensitivity, specificity, linearity, and interferences.
UNASSIGNED: 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.
UNASSIGNED: 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.