Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid

Two key arsenic metabolites, monomethylarsonous acid (MMA(III)) and dimethy larsinous acid (DMA(III)), have recently been detected in human urine. Ther e is an increasing interest in the speciation of these metabolites in human s because of their demonstrated effects on cellular toxicity and DNA damage . However, there is no information on the oxidative stability of these arse nic species. It is not known whether and to what extent these trivalent met abolites are changed during sample handling and storage. The objective of t his study was to demonstrate the oxidative conversion of these arsenic spec ies during sample storage. We compared the effects of the storage temperatu re (25, 4, and -20 degreesC) and storage duration (up to 5 months) on the s tability of MMA(III) and DMA(III) in de-ionized water and in human urine. W e used HPLC with hydride generation atomic fluorescence detection for the s peciation of arsenic. This method provided sub-mug L-1 to low-mug L-1 detec tion limits for each arsenic species. We found that the oxidation of MMA(II I) and DMA(III) was matrix and temperature dependent. Low temperature condi tions (4 and -20 degreesC) improved the stability of these arsenic species over the room temperature storage condition. MMA(III) in de-ionized water w as 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 wate r 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 degrees C. The conversion of DMA(III) to DMA(V) in urine at 25 degreesC was complet e in 17 h. These results show that MMA(III) and DMA(III) are much less stab le than other arsenic species, and their stability depends on sample matrix and temperature.