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一种用于环磷酰胺治疗药物监测的高特异性免疫分析法。

A high-specificity immunoassay for the therapeutic drug monitoring of cyclophosphamide.

机构信息

Nanobiotechnology for Diagnostics (Nb4D), Department of Surfactants and Nanobiotechnology (SNT), Institute for Advanced Chemistry of Catalonia (IQAC) of the Spanish Council for Scientific Research (CSIC), Spain.

出版信息

Analyst. 2019 Aug 16;144(17):5172-5178. doi: 10.1039/c9an00576e.

DOI:10.1039/c9an00576e
PMID:31343645
Abstract

Personalized medicine is pushing forward new diagnostic techniques to aid in controlling drug therapeutic levels and their toxic effects. This study aims to develop a high-throughput screening method for therapeutic drug monitoring (TDM) and occupational exposure of cyclophosphamide (CP), an alkylating agent used as a chemotherapeutic and immunosuppressive drug. In order to achieve this goal, an immunizing hapten that exposes the cyclophosphamide moiety has been designed for the first time. Antibodies produced against this hapten have been used to develop an indirect competitive ELISA for the quantification of CP with high specificity and low cross-reactivity with some metabolites and other anticancer drugs. The assay obtained showed a LOD of 22 ± 6 nM in serum samples, with concentrations much below the blood CP levels of patients treated with the drug. A new tool for the detection and quantification of CP is provided which could be relevant for future pharmacokinetic studies and for therapeutic index improvement.

摘要

个体化医学正在推动新的诊断技术,以帮助控制药物治疗水平及其毒副作用。本研究旨在开发一种用于治疗药物监测 (TDM) 和职业接触的高通量筛选方法,所用药物为环磷酰胺 (CP),这是一种烷化剂,用作化疗和免疫抑制剂。为了实现这一目标,首次设计了一种暴露环磷酰胺部分的免疫半抗原。针对该半抗原产生的抗体已被用于开发间接竞争 ELISA,用于定量检测 CP,具有高特异性和低交叉反应性,与一些代谢物和其他抗癌药物无交叉反应。该测定法在血清样本中的检测限为 22 ± 6 nM,浓度远低于接受该药物治疗的患者的血液 CP 水平。提供了一种用于检测和定量 CP 的新工具,这可能与未来的药代动力学研究和治疗指数改善相关。

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