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采用稳定同位素稀释气相色谱-负离子化学电离质谱法(GC-NICIMS)分析人血浆中的5-氟尿嘧啶。

The analysis of 5-fluorouracil in human plasma by gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICIMS) with stable isotope dilution.

作者信息

Bates C D, Watson D G, Willmott N, Logan H, Goldberg J

机构信息

Department of Pharmacy, University of Strathclyde, Glasgow, UK.

出版信息

J Pharm Biomed Anal. 1991;9(1):19-21. doi: 10.1016/0731-7085(91)80231-w.

DOI:10.1016/0731-7085(91)80231-w
PMID:2043717
Abstract

5-Fluorouracil (5-FU) was extracted from plasma and converted to its di-N-ditrifluoromethylbenzyl (DTFMBz) derivative by treatment with DTFMBzBr. Under negative ion chemical ionization (NICI) conditions the derivative yielded a mass spectrum in which most of the ion current was carried by the M(-)-DTFMBz ion (m/z 355). Selected ion monitoring enabled detection of this derivative in amounts less than 1 pg, and the practical limit of detection for 5-FU extracted from plasma was ca 400 pg ml-1. 5-FU was quantified by adding a fixed amount of [15N2]5-FU to samples of plasma before extraction, and comparing the ratio of the ions of m/z 355 and 357 against a calibration curve constructed over the concentration range under investigation. The method was used to measure the variation in the concentration of 5-FU with time during continuous infusion of the drug via three, different protocols in patients with hepatic tumour.

摘要

从血浆中提取5-氟尿嘧啶(5-FU),并用二-N-二(三氟甲基)苄基溴(DTFMBzBr)处理将其转化为其二-N-二(三氟甲基)苄基(DTFMBz)衍生物。在负离子化学电离(NICI)条件下,该衍生物产生的质谱中大部分离子流由M(-)-DTFMBz离子(m/z 355)携带。选择离子监测能够检测到量少于1 pg的该衍生物,从血浆中提取的5-FU的实际检测限约为400 pg ml-1。通过在提取前向血浆样品中加入固定量的[15N2]5-FU,并将m/z 355和357离子的比率与在所研究浓度范围内构建的校准曲线进行比较,对5-FU进行定量。该方法用于测量通过三种不同方案对肝肿瘤患者持续输注药物期间5-FU浓度随时间的变化。

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引用本文的文献

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Derivatization of 5-fluorouracil with 4-bromomethyl-7-methoxycoumarin for determination by liquid chromatography-mass spectrometry.用4-溴甲基-7-甲氧基香豆素对5-氟尿嘧啶进行衍生化,用于液相色谱-质谱联用测定。
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