Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18057 Rostock, Germany.
Clinic for Hematology, Oncology and Palliative Care, Rostock University Medical Center, 18057 Rostock, Germany.
Molecules. 2022 Apr 7;27(8):2394. doi: 10.3390/molecules27082394.
Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract cancer. Silmitasertib inhibits the serine/threonine protein kinase CK2, which exerts a proliferation-promoting and anti-apoptotic effect on cancer cells. In view of current and future applications, the measurement of silmitasertib levels in plasma is expected to play an important role in the evaluation of therapeutic and toxic concentrations in cancer patients. In the present work, we therefore present an LC-MS/MS method for the quantification of silmitasertib in human plasma. Using a simple liquid-liquid extraction with ethyl acetate and a mixture of n-hexane and ethyl acetate, this method can be performed in any laboratory with mass spectrometry. The validation was carried out according to the FDA guideline.
西利美坦（CX-4945）目前正在针对各种类型的癌症进行临床试验。美国食品和药物管理局（FDA）已授予该化合物孤儿药认定，用于治疗晚期胆管癌、髓母细胞瘤和胆道癌。西利美坦抑制丝氨酸/苏氨酸蛋白激酶 CK2，该激酶对癌细胞具有促进增殖和抗凋亡作用。鉴于目前和未来的应用，血浆中西利美坦水平的测量有望在评估癌症患者的治疗和毒性浓度方面发挥重要作用。在本工作中，我们因此提出了一种 LC-MS/MS 方法，用于定量检测人血浆中的西利美坦。该方法采用乙酸乙酯的简单液-液萃取，以及正己烷和乙酸乙酯的混合物，任何具有质谱的实验室都可以进行该方法。验证是根据 FDA 指南进行的。
