Abstract：
Vistusertib is an orally bioavailable mTOR inhibitor that is being studied in clinical trials. A novel reliable method was developed to quantitate vistusertib using LC-MS/MS to explore drug exposure-response relationships. Sample preparation involved protein precipitation using acetonitrile. Separation of vistusertib and the internal standard, AZD8055, was achieved with a Waters Acquity UPLC BEH C18 column utilizing isocratic elution over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of vistusertib. The assay range was 5-5000 ng/mL and proved to be accurate (98.7-105.7%) and precise (CV ≤ 10.5%). A 40,000 ng/mL sample that was diluted 1:10 (v/v) with plasma was accurately quantitated. Long-term frozen plasma stability for vistusertib at -70 °C has been determined for at least 29 months. The method was applied for the measurement of plasma concentrations of vistusertib in a patient a solid tumor receiving 35 mg twice daily dose orally.
摘要：
Vistusertib是一种口服生物可利用的mTOR抑制剂，正在临床试验中进行研究。开发了一种新的可靠方法来使用LC-MS/MS定量vistusertib，以探索药物暴露-反应关系。样品制备涉及使用乙腈的蛋白质沉淀。分离vistusertib和内标，AZD8055是使用WatersAcquityUPLCBEHC18柱在3分钟的总分析运行时间内利用等度洗脱实现的。使用以正电喷雾电离模式操作的SCIEX4500三重四极质谱仪检测vistusertib。测定范围为5-5000ng/mL，被证明是准确的（98.7-105.7％）和精确的（CV≤10.5％）。精确定量用血浆1:10(v/v)稀释的40,000ng/mL样品。已确定vistusertib在-70°C下的长期冷冻血浆稳定性至少29个月。该方法用于测量接受35mg每日两次口服剂量的实体瘤患者中vistusertib的血浆浓度。
