Liu Xin, Hummon Amanda B
Department of Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN, 46556, USA.
J Am Soc Mass Spectrom. 2015 Apr;26(4):577-86. doi: 10.1007/s13361-014-1071-0. Epub 2015 Jan 21.
A new and simple method was developed to evaluate the distribution of therapeutics in three-dimensional multicellular tumor spheroids (MCTS) by combining serial trypsinization and nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS). This methodology was validated with quantitative measurements of irinotecan and its bioactive metabolite, SN-38, in distinct spatial regions of HCT 116 MCTS. Irinotecan showed a time-dependent permeability into MCTS with most of the drug accumulating in the core after 24 h of treatment. The amount of SN-38 detected was 30 times lower than that of the parent drug, and was more abundant in the outer rim and intermediate regions of MCTS where proliferating cells were present. This method can be used to investigate novel and established drugs. It enables investigation of drug penetration properties and identification of metabolites with spatial specificity in MCTS. The new approach has great value in facilitating the drug evaluation process.
通过结合连续胰蛋白酶消化和纳流液相色谱-串联质谱法（nLC-MS/MS），开发了一种新的简单方法来评估治疗药物在三维多细胞肿瘤球体（MCTS）中的分布。该方法通过对伊立替康及其生物活性代谢物SN-38在HCT 116 MCTS不同空间区域的定量测量进行了验证。伊立替康在MCTS中的渗透性呈现时间依赖性，治疗24小时后，大部分药物积聚在核心区域。检测到的SN-38量比母体药物低30倍，并且在存在增殖细胞的MCTS外边缘和中间区域更为丰富。该方法可用于研究新型药物和已上市药物。它能够研究药物的渗透特性，并在MCTS中进行具有空间特异性的代谢物鉴定。这种新方法在促进药物评估过程方面具有重要价值。
