PDF(Pubmed)
Abstract：
Despite the considerable steps taken in the last decade in the context of antineoplastic drug (AD) handling procedures, their mutagenic effect still poses a threat to healthcare personnel actively involved in compounding and administration units. Biological monitoring procedures usually require large volumes of sample and extraction solvents, or do not provide adequate sensitivity. It is here proposed a fast and automated method to evaluate the urinary levels of cyclophosphamide and iphosphamide, composed of a miniaturized solid phase extraction (µSPE) followed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The extraction procedure, developed through design of experiments (DoE) on the ePrep One Workstation, required a total time of 9.5 min per sample, with recoveries of 77-79% and a solvent consumption lower than 1.5 mL per 1 mL of urine sample. Thanks to the UHPLC-MS/MS method, the limits of quantification (LOQ) obtained were lower than 10 pg/mL. The analytical procedure was successfully applied to 23 urine samples from compounding wards of four Italian hospitals, which resulted in contaminations between 27 and 182 pg/mL.
摘要：
尽管在过去十年中在抗肿瘤药物（AD）处理程序方面采取了相当大的步骤，它们的诱变效应仍然对积极参与复合和管理单位的医护人员构成威胁。生物监测程序通常需要大量的样品和提取溶剂，或者没有提供足够的灵敏度。这里提出了一种快速，自动化的方法来评估环磷酰胺和磷酰胺的尿水平，由小型化固相萃取（µSPE）组成，然后进行超高效液相色谱-串联质谱（UHPLC-MS/MS）分析。提取程序，通过ePrepOne工作站上的实验设计(DoE)开发，每个样品需要9.5分钟的总时间，回收率为77-79％，每1mL尿液样品的溶剂消耗量低于1.5mL。由于UHPLC-MS/MS方法，获得的定量限（LOQ）低于10pg/mL。该分析程序已成功应用于意大利四家医院复合病房的23份尿液样本，这导致27和182pg/mL之间的污染。
