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Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces

机译:擦拭采样程序结合LC-MS / MS分析,可同时测定不同表面上的10种细胞毒性药物

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摘要

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm ~(-2)) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.
机译:开发了一种简单的擦拭取样程序,用于测定十种细胞毒性药物的表面污染:阿糖胞苷,吉西他滨,甲氨蝶呤,依托泊苷磷酸盐,环磷酰胺,异环磷酰胺,伊立替康,阿霉素,表柔比星和长春新碱。使用Whatman滤纸在不同表面(例如,不锈钢,聚丙烯,聚苯乙烯,玻璃,乳胶手套,计算机鼠标和涂层纸板)上进行擦拭。研究了擦拭和解吸程序:在水中含有20%乙腈和0.1%甲酸的相同溶液给出了最佳结果。超声解吸然后离心后,在选定的反应监测模式下,通过经过验证的液相色谱-串联质谱分析(LC-MS / MS)分析样品。评估了从擦拭取样到LC-MS / MS分析的整个分析策略,以确定定量性能。对于十种研究的细胞毒性药物,确定了每个擦拭样品10 ng(即0.1 ng cm〜(-2))的最低定量限。中等精度的相对标准偏差始终小于20%。由于每种药物的回收率取决于测试表面,因此确定了校正因子并将其应用于真实样品。然后,该方法已成功应用于日内瓦大学医院药房的细胞毒性生产部门。

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