MICRODIALYSIS/MASS SPECTROMETRY

微量透析/质谱分析

• 批准号: 3855930
• 负责人: K B TOMER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855930
• 关键词: analytical method; chemical carcinogen; dialysis; halocarbon compound; high performance liquid chromatography; laboratory rat; mass spectrometry; phosphorus compounds; radiotracer

Microdialysis is a relatively new sampling technique designed for the in vivo analysis of endobiotic/xenobiotic substances. The microdialysis probe is surgically implanted into a vein or a tissue of interest in an animal. Substances within the bloodstream or tissue with Mr below the molecular weight cutoff of the dialysis membrane dialyze across the membrane into the perfusate. We have interfaced this technique-with mass spectral analysis using the coaxial continuous flow fast atom bombardment (CF-FAB) approach we have developed and tandem mass spectrometry. In our initial experiments, we have investigated the half-life of the suspected carcinogen tris (2-chloroethyl)phosphate in the blood of rats. Tris organophosphates have been widely used in plastics and synthetic fibers as flame retardants. We have been able to determine that the half-life of this compound in blood follows a two compartment model. The alpha half-life (due to distribution and elimination) is 2.9 min. while the beta half-life (due to elimination only) is 23 min. There was no statistical difference (T-test) between these results and those of HPLC analyses using radiotracers. As an indication of the sensitivity of the technique, after one hour, the tris concentration in the blood is approximately 20 micromolar. The signal-to-noise ratio of the MS/MS signal at this time was greater than 10:1.

微透析是一种相对较新的采样技术， 内源性/外源性物质的体内分析。 微透析探针 通过外科手术植入到动物的静脉或感兴趣的组织中。 血流或组织中Mr低于分子量的物质 透析膜的截留重量透析穿过膜进入 灌注液 我们已经将这项技术与质谱分析相结合 使用同轴连续流快原子轰击（CF-FAB）方法 我们开发了串联质谱法。 在我们最初的实验中，我们研究了 大鼠血液中的疑似致癌物磷酸三（2-氯乙基）酯。 三聚磷酸三酯已广泛应用于塑料和合成 纤维作为阻燃剂。 我们已经能够确定 该化合物在血液中的半衰期遵循二室模型。 的 α半衰期（由于分布和消除）为2.9分钟，而 β半衰期（仅由于消除）为23分钟。 这些结果与HPLC结果之间的统计学差异（T检验） 使用放射性示踪剂进行分析。 作为敏感性的指示， 技术，一小时后，血液中的三羟甲基氨基甲烷浓度为 大约20微摩尔。 MS/MS信号的信噪比 当时的比例大于10：1。