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采用 ICP-MS 测定人尿液中来源于镓的抗癌药物中的镓。

Determination of gallium originated from a gallium-based anticancer drug in human urine using ICP-MS.

机构信息

Division of Analytical Chemistry, Chemistry Department, Moscow State University, Russia.

出版信息

Anal Bioanal Chem. 2011 May;400(3):709-14. doi: 10.1007/s00216-011-4791-z. Epub 2011 Mar 1.

Abstract

Urine analysis gives an insight into the excretion of the administered drug which is related to its reactivity and toxicity. In this work, the capability of inductively coupled plasma mass spectrometry (ICP-MS) to measure ultratrace metal levels was utilized for rapid assaying of gallium originating from the novel gallium anticancer drug, tris(8-quinolinolato)gallium(III) (GaQ(3)), in human urine. Sample dilution with 1% (v/v) HNO(3) as the only required pre-treatment was shown to prevent contamination of the sample introduction system and to reduce polyatomic interferences from sample components. The origin of the blank signal at masses of gallium isotopes, 71 and 69, was investigated using high-resolution ICP-MS and attributed, respectively, to the formation of (36)Ar(35)Cl(+) and (40)Ar(31)P(+) ions and, tentatively, to a triplet of doubly charged ions of Ba, La, and Ce. The accuracy and precision performance was tested by evaluating a set of parameters for analytical method validation. The developed assay has been applied for the determination of gallium in urine samples spiked with GaQ(3). The achieved recoveries (95-102%) and quantification limit of 0.2 μg L(-1) emphasize the practical applicability of the presented analytical approach to monitor renal elimination of GaQ(3) at all dose levels in clinical trials that are currently in progress.

摘要

尿液分析可深入了解所摄入药物的排泄情况,这与药物的反应性和毒性有关。在这项工作中,我们利用电感耦合等离子体质谱(ICP-MS)来测量痕量金属水平的能力,快速测定新型镓抗癌药物三(8-喹啉基)镓(III)(GaQ(3))在人尿中的含量。结果表明,用 1%(v/v)HNO(3)稀释样品作为唯一需要的预处理,可以防止样品引入系统受到污染,并减少样品成分的多原子干扰。使用高分辨率 ICP-MS 研究了 Ga 同位素(71 和 69)质量处的空白信号的来源,并分别归因于(36)Ar(35)Cl(+)和(40)Ar(31)P(+)离子的形成,以及暂定的 Ba、La 和 Ce 的三重双电荷离子。通过评估一组分析方法验证参数来测试准确性和精密度性能。所开发的测定方法已应用于加标 GaQ(3)的尿样中 Ga 的测定。所获得的回收率(95-102%)和定量限为 0.2 μg L(-1),强调了所提出的分析方法在目前正在进行的临床试验中监测 GaQ(3)在所有剂量水平下的肾排泄的实际适用性。

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