Le X C, Lu X, Ma M, Cullen W R, Aposhian H V, Zheng B
Department of Public Health Sciences, University of Alberta, Edmonton, Canada.
Anal Chem. 2000 Nov 1;72(21):5172-7. doi: 10.1021/ac000527u.
Biomethylation is the major human metabolic pathway for inorganic arsenic, and the speciation of arsenic metabolites is essential to a better understanding of arsenic metabolism and health effects. Here we describe a technique for the speciation of arsenic in human urine and demonstrate its application to the discovery of key arsenic metabolic intermediates, monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII), in human urine. The study provides a direct evidence in support of the proposed arsenic methylation pathway in the human. The finding of MMAIII and DMAIII in human urine, along with recent studies showing the high toxicity of these arsenicals, suggests that the usual belief of arsenic detoxification by methylation needs to be reconsidered. The arsenic speciation technique is based on ion pair chromatographic separation of arsenic species on a 3-micron particle size column at 50 degrees C followed by hydride generation atomic fluorescence detection. Speciation of MMAIII, DMAIII, arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in urine samples is complete in 6 min with detection limits of 0.5-2 micrograms/L. There is no need for any sample pretreatment. The capability of rapid analysis of trace levels of arsenic species, which resulted in the findings of the key metabolic intermediates, makes the technique useful for routine arsenic speciation analysis required for toxicological and epidemiological studies.
生物甲基化是人体对无机砷的主要代谢途径，砷代谢产物的形态对于更好地理解砷代谢及健康影响至关重要。在此，我们描述了一种用于测定人尿中砷形态的技术，并展示了其在发现人尿中关键砷代谢中间体——一甲基亚胂酸（MMAIII）和二甲基亚胂酸（DMAIII）方面的应用。该研究为所提出的人体砷甲基化途径提供了直接证据。在人尿中发现MMAIII和DMAIII，以及近期研究表明这些砷化物具有高毒性，这表明通常认为通过甲基化进行砷解毒的观点需要重新审视。砷形态分析技术基于在50℃下于3微米粒径的色谱柱上对砷形态进行离子对色谱分离，随后进行氢化物发生原子荧光检测。尿样中MMAIII、DMAIII、亚砷酸盐（AsIII）、砷酸盐（AsV）、一甲基砷酸（MMAV）和二甲基砷酸（DMAV）的形态分析在6分钟内完成，检测限为0.5 - 2微克/升。无需任何样品预处理。能够快速分析痕量水平的砷形态，从而发现关键代谢中间体，使得该技术可用于毒理学和流行病学研究所需的常规砷形态分析。
