Experimental and Clinical Pharmacology Unit, National Cancer Institute - Centro di Riferimento Oncologico, Via Franco Gallini 2, I-33081, Aviano, Italy.
Experimental and Clinical Pharmacology Unit, National Cancer Institute - Centro di Riferimento Oncologico, Via Franco Gallini 2, I-33081, Aviano, Italy.
J Pharm Biomed Anal. 2018 Sep 10;159:73-81. doi: 10.1016/j.jpba.2018.06.032. Epub 2018 Jun 21.
The implementation of therapeutic drug monitoring in the routine clinical practice in oncology is mainly limited by the lack of therapeutic indexes for the majority of the anticancer drugs, and by the absence of suitable analytical tools, which can accurately quantify in real time the concentration of the administered drugs and their relevant metabolites in biological fluids. In this work, a simple and efficient fluorimetric determination of SN-38, the active metabolite of the anticancer drug irinotecan, was developed and applied to human plasma samples. The intrinsic fluorescence of SN-38 allowed its quantification in the range 10-500 ng mL with a LOQ of 5.0 ng mL and a LOD of 1.5 ng mL. Low interferences due to main metabolites of irinotecan and comedications, commonly associated with administration of irinotecan, were observed. A validation study, according to FDA and EMA guidelines for bioanalytical method validation, was carried out and, finally, blind samples were analyzed in parallel with a HPLC-MS method obtaining an excellent agreement between the two techniques.
大多数抗癌药物缺乏治疗指数，并且缺乏合适的分析工具，这些工具无法实时准确地定量检测生物体液中给予的药物及其相关代谢物的浓度。在这项工作中，开发了一种简单高效的荧光测定法来测定抗癌药物伊立替康的活性代谢物 SN-38，并将其应用于人血浆样品中。SN-38 的本征荧光使其能够在 10-500ng/mL 的范围内进行定量，LOQ 为 5.0ng/mL，LOD 为 1.5ng/mL。观察到由于伊立替康的主要代谢物和与伊立替康给药相关的联合用药产生的低干扰。根据 FDA 和 EMA 生物分析方法验证指南进行了验证研究，最后，用 HPLC-MS 方法平行分析了盲样，两种技术之间具有极好的一致性。
