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通过流动注射-电喷雾串联质谱法分析10B抗肿瘤化合物。

Analysis of 10B antitumoral compounds by means of flow-injection into ESI-MS/MS.

作者信息

Basilico F, Sauerwein W, Pozzi F, Wittig A, Moss R, Mauri P L

机构信息

Istituto Tecnologie Biomediche, via Fratelli Cervi, 93, Segrate, Milan, Italy.

出版信息

J Mass Spectrom. 2005 Dec;40(12):1546-9. doi: 10.1002/jms.909.

Abstract

Boron neutron capture therapy (BNCT) is a promising binary treatment for cancer. BNCT is based on the ability of the nonradioactive isotope (10)B to capture, with a very high probability, thermal neutrons. This nuclear reaction results in two particles (an alpha and a lithium nucleus). The particles have a high biological effectiveness, which is limited in tissue to approximately the diameter of one cell. If the reaction can be limited to a tumor cell, the physical characteristic opens up the possibility to selectively destroy cancer cells, while sparing the surrounding healthy tissue. Quality control of (10)B-containing compounds and their distribution at present are very important, and different analytical methods have been developed, such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), electron energy loss spectrometry (EELS), prompt gamma analysis and inductively coupled plasma-optical emission spectrometry (ICP-OES). These methods allow the analyses of (10)B, but it is not possible to characterize the specific molecular compounds containing (10)B. For this reason, we propose a fast and quantitative method that permits the determination of closo-undecahydro-1-mercaptododecaborate (BSH) and (10)boron-phenylalanine (BPA) and their eventual metabolites. In particular, (10)B-containing compounds are detected by means of flow-injection electrospray tandem mass spectrometry (FI/ESI-MS/MS). This approach allows the identification of Boron compounds, BSH and BPA, using tandem mass spectrometry, and quantitative analysis is also possible (c.v. +/-4.7%; n = 5; linear range 10-10,000 ng/ml). Furthermore, (10)B-containing compounds were detected in actual biological sample (urine and plasma, diluted 10,000- and 1,000-fold, respectively) injecting a small volume (1 microl) of diluted samples.

摘要

硼中子俘获疗法(BNCT)是一种很有前景的癌症二元治疗方法。BNCT基于非放射性同位素硼-10(¹⁰B)以非常高的概率俘获热中子的能力。这种核反应产生两个粒子(一个α粒子和一个锂核)。这些粒子具有很高的生物有效性,在组织中的作用范围大约局限于一个细胞的直径。如果该反应能够局限于肿瘤细胞,这种物理特性就为选择性地破坏癌细胞同时 sparing the surrounding healthy tissue. Quality control of (10)B-containing compounds and their distribution at present are very important, and different analytical methods have been developed, such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), electron energy loss spectrometry (EELS), prompt gamma analysis and inductively coupled plasma-optical emission spectrometry (ICP-OES). These methods allow the analyses of (10)B, but it is not possible to characterize the specific molecular compounds containing (10)B. For this reason, we propose a fast and quantitative method that permits the determination of closo-undecahydro-1-mercaptododecaborate (BSH) and (10)boron-phenylalanine (BPA) and their eventual metabolites. In particular, (10)B-containing compounds are detected by means of flow-injection electrospray tandem mass spectrometry (FI/ESI-MS/MS). This approach allows the identification of Boron compounds, BSH and BPA, using tandem mass spectrometry, and quantitative analysis is also possible (c.v. +/-4.7%; n = 5; linear range 10-10,000 ng/ml). Furthermore, (10)B-containing compounds were detected in actual biological sample (urine and plasma, diluted 10,000- and 1,000-fold, respectively) injecting a small volume (1 microl) of diluted samples.

保留周围健康组织创造了可能性。目前,含硼-10化合物的质量控制及其分布非常重要,并且已经开发了不同的分析方法,如飞行时间二次离子质谱法(TOF-SIMS)、电子能量损失谱法(EELS)、瞬发伽马分析和电感耦合等离子体发射光谱法(ICP-OES)。这些方法能够分析硼-10,但无法表征含硼-10的特定分子化合物。因此,我们提出了一种快速定量方法,可用于测定闭式十一氢-1-巯基十二硼酸盐(BSH)和硼-10-苯丙氨酸(BPA)及其最终代谢产物。特别是,通过流动注射电喷雾串联质谱法(FI/ESI-MS/MS)检测含硼-10的化合物。这种方法利用串联质谱法能够鉴定硼化合物、BSH和BPA,并且也可以进行定量分析(变异系数±4.7%;n = 五;线性范围10 - 10000 ng/ml)。此外,通过注入少量(1微升)稀释样品,在实际生物样品(尿液和血浆,分别稀释10000倍和1000倍)中检测到了含硼-10的化合物。 (你提供的英文原文中“sparing the surrounding healthy tissue.”后面内容似乎不完整且表述混乱,我按照现有内容尽量准确翻译了。)

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