Institute of Pharmacology and Toxicology, Rostock University Medical Centre, 18057 Rostock, Germany.
Clinic for Hematology, Oncology and Palliative Care, Rostock University Medical Centre, 18057 Rostock, Germany.
Molecules. 2022 Feb 1;27(3):974. doi: 10.3390/molecules27030974.
The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine-threonine kinase glycogen synthase kinase 3β SB216763, has shown preclinical antitumour effects in various cell lines, with the key pathways of its anticancer activity being cell cycle modulation, DNA replication and p53 signalling. For the monitoring of anticancer drug treatment in the context of therapeutic drug monitoring, the determination of plasma concentrations is essential, for which an LC-MS/MS method is particularly suitable. In the present study, a sensitive LC-MS/MS method for the quantification of the potential anticancer drug PDA-66 in human plasma with a lower limit of quantification of 2.5 nM is presented. The method was successfully validated and tested for the determination of PDA-66 in mouse plasma and sera.
癌症的治疗是药理学上最重要的挑战之一。为此，一段时间以来，化疗已通过针对特定结构的靶向治疗得到补充。PDA-66 是丝氨酸-苏氨酸激酶糖原合成酶激酶 3β 的抑制剂 SB216763 的结构类似物，已在各种细胞系中显示出抗肿瘤作用，其抗癌活性的关键途径是细胞周期调节、DNA 复制和 p53 信号传导。为了在治疗药物监测的背景下监测抗癌药物治疗，监测血浆浓度至关重要，为此，液相色谱-串联质谱法 (LC-MS/MS) 特别适用。本研究提出了一种灵敏的 LC-MS/MS 方法，用于定量检测人血浆中的潜在抗癌药物 PDA-66，其定量下限为 2.5 nM。该方法已成功验证并用于检测小鼠血浆和血清中的 PDA-66。
