Development and validation of an UPLC-ESI-MS/MS method for simultaneous quantification of antineoplastic agents and their metabolites in human plasma after unintentional exposure.

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-10-31 DOI:10.1007/s00204-024-03900-5
Eline Verscheure, Ilana Struys, Matteo Creta, Katrien Poels, Jeroen Vanoirbeek, Liesbeth Lenaerts, Frédéric Amant, Manosij Ghosh, Lode Godderis
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Abstract

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.

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开发并验证一种 UPLC-ESI-MS/MS 方法,用于同时定量无意接触后人体血浆中的抗肿瘤药物及其代谢物。
环磷酰胺、daunorubicin、表柔比星、多柔比星和紫杉醇是治疗癌症的常用药物。然而,目前还没有能够同时测量人体血浆中这些化合物及其代谢物的方法。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。样品净化采用 Oasis PRiME HLB 固相萃取柱。样品经 Acquity UPLC BEH C18 色谱柱分离,电喷雾离子化,串联质谱检测。根据选择性、萃取效率、基质效应、过程效率、线性、灵敏度、精密度和准确度对该方法进行了验证。确定的最低检出限为 0.05 纳克/毫升(环磷酰胺)、30 纳克/毫升(4-氧代环磷酰胺)、0.3 纳克/毫升(多柔比星、多诺比星醇)、0.7 纳克/毫升(表柔比星、表柔比星醇、多柔比星醇)、1 纳克/毫升(多柔比星和紫杉醇)和 5 纳克/毫升(6-α-羟基紫杉醇)。随后,该方法在实际生活中的无意暴露环境中进行了测试。对 22 份血浆样本进行了分析,这些样本来自接受化疗的妊娠期癌症患者的配对母血和脐带血。结果有两个样本呈阳性,环磷酰胺浓度高达 0.37 纳克/毫升。经过验证的方法现已可以在实地应用。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening. The emerging role of alternatively activated macrophages to treat acute liver injury. Development and validation of an UPLC-ESI-MS/MS method for simultaneous quantification of antineoplastic agents and their metabolites in human plasma after unintentional exposure. Telmisartan potentiates the ITE-induced aryl hydrocarbon receptor activity in human liver cell line. Therapeutic potential of 4-phenylbutyric acid against methylmercury-induced neuronal cell death in mice.
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