Verscheure Eline, Struys Ilana, Creta Matteo, Poels Katrien, Vanoirbeek Jeroen, Lenaerts Liesbeth, Amant Frédéric, Ghosh Manosij, Godderis Lode
Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Department of Oncology, KU Leuven, Herestraat 49, 3000, Louvain, Belgium.
Arch Toxicol. 2025 Jan;99(1):259-270. doi: 10.1007/s00204-024-03900-5. Epub 2024 Oct 31.
Cyclophosphamide, daunorubicin, epirubicin, doxorubicin and paclitaxel are commonly used drugs in cancer treatment. However, there are no methods available enabling simultaneous measurement of these compounds and their metabolites in human plasma. Our aim was to develop and validate a sensitive method for simultaneous quantification of multiple antineoplastic drugs and their major metabolites in plasma. Solid phase extraction with Oasis PRiME HLB cartridges was used for sample clean-up. The samples were separated on an Acquity UPLC BEH C18 column, ionised by electrospray ionisation and detected with tandem mass spectrometry. The method was validated based on selectivity, extraction efficiency, matrix effect, process efficiency, linearity, sensitivity, precision and accuracy. The established LLOQs were 0.05 ng/mL (cyclophosphamide), 30 ng/mL (4-oxo-cyclophosphamide), 0.3 ng/mL (doxorubicin, daunorubicinol), 0.7 ng/mL (epirubicin, epirubicinol, doxorubicinol), 1 ng/mL (daunorubicin and paclitaxel) and 5 ng/mL (6-alpha-hydroxypaclitaxel). Afterwards, the method was tested in a real-life, unintentional exposure setting. Twenty-two plasma samples of matched maternal and cord blood pairs from pregnant cancer patients treated with chemotherapy were analysed. This resulted in two positive samples, with cyclophosphamide concentrations up to 0.37 ng/mL. The validated method is now ready to be applied in the field.
环磷酰胺、柔红霉素、表柔比星、多柔比星和紫杉醇是癌症治疗中常用的药物。然而，目前尚无能够同时测定这些化合物及其在人血浆中代谢物的方法。我们的目的是开发并验证一种灵敏的方法，用于同时定量血浆中的多种抗肿瘤药物及其主要代谢物。使用Oasis PRiME HLB柱进行固相萃取以净化样品。样品在Acquity UPLC BEH C18柱上分离，通过电喷雾电离进行离子化，并采用串联质谱进行检测。该方法基于选择性、萃取效率、基质效应、过程效率、线性、灵敏度、精密度和准确度进行验证。确定的定量下限分别为：0.05 ng/mL（环磷酰胺）、30 ng/mL（4-氧代环磷酰胺）、0.3 ng/mL（多柔比星、柔红霉醇）、0.7 ng/mL（表柔比星、表柔比星醇、多柔比星醇）、1 ng/mL（柔红霉素和紫杉醇）以及5 ng/mL（6-α-羟基紫杉醇）。之后，该方法在实际意外暴露情况下进行了测试。分析了22对接受化疗的孕妇癌症患者的配对母血和脐血血浆样本。结果有两个阳性样本，环磷酰胺浓度高达0.37 ng/mL。现已验证的该方法可应用于实际领域。
