Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid

Two key arsenic metabolites, monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), have recently been detected in human urine. There is an increasing interest in the speciation of these metabolites in humans because of their demonstrated effects on cellular toxicity and DNA damage. However, there is no information on the oxidative stability of these arsenic species. It is not known whether and to what extent these trivalent metabolites are changed during sample handling and storage. The objective of this study was to demonstrate the oxidative conversion of these arsenic species during sample storage. We compared the effects of the storage temperature (25, 4, and -20 degreesC) and storage duration (up to 5 months) on the stability of MMA(III) and DMA(III) in de-ionized water and in human urine. We used HPLC with hydride generation atomic fluorescence detection for the speciation of arsenic. This method provided sub-mug L-1 to low-mug L-1 detection limits for each arsenic species. We found that the oxidation of MMA(III) and DMA(III) was matrix and temperature dependent. Low temperature conditions (4 and -20 degreesC) improved the stability of these arsenic species over the room temperature storage condition. MMA(III) in de-ionized water was relatively stable for almost 4 months, when stored at 4 or -20 degreesC with less than 10% of MMA(III) oxidized to MMA(V). In contrast, most of MMA(III) ( 90%) in urine was oxidized to MMA(V) over the 5 month period under the 4 or -20 degreesC storage condition. At 25 degreesC, MMA(III) in urine was completely oxidized to MMA(V) within a week. DMA(III) in deionized water was stable for only 2-3 days, being rapidly oxidized to DMA(V). DMA(III) in urine was completely oxidized to DMA(V) within a day at 4 or -20 degreesC. The conversion of DMA(III) to DMA(V) in urine at 25 degreesC was complete in 17 h. These results show that MMA(III) and DMA(III) are much less stable than other arsenic species, and their stability depends on sample matrix and temperature.