Speciation of key arsenic metabolic intermediates in human urine

Biomethylation is the major human metabolic pathway for inorganic arsenic, and the speciation of arsenic metabolites is essential to a better understa nding of arsenic metabolism and health effects. Here we describe a techniqu e for the speciation of arsenic in human urine and demonstrate its applicat ion to the discovery of key arsenic metabolic intermediates, monomethylarso nous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), in human urine. The study provides a direct evidence in support of the proposed arsenic met hylation pathway in the human. The finding of MMA(III) and DMA(III) in huma n urine, along with recent studies showing the high toxicity of these arsen icals, suggests that the usual belief of arsenic detoxification by methylat ion needs to be reconsidered, The arsenic speciation technique is based on ion pair chromatographic separation of arsenic species on a 3-mum particle size column at 50 degreesC followed by hydride generation atomic fluorescen ce detection. Speciation of MMA(III), DMA(III), arsenite (As-III), arsenate (As-V), monomethylarsonic acid(MMA(V)), and dimethylarsinic acid (DMA(V)) in urine samples is complete in 6 min with detection limits of 0.5-2 mug/L. There is no need for any sample pretreatment. The capability of rapid anal ysis of trace levels of arsenic species, which resulted in the findings of the key metabolic intermediates, makes the technique useful for routine ars enic speciation analysis required for toxicological and epidemiological stu dies.