@article {386, title = {Determination of arsenic metabolic complex excreted in human urine after administration of sodium 2,3-dimercapto-1-propane sulfonate}, journal = {Chemical Research in Toxicology}, volume = {15}, number = {10}, year = {2002}, note = {ISI Document Delivery No.: 607TXTimes Cited: 15Cited Reference Count: 42}, month = {Oct}, pages = {1318-1323}, type = {Article}, abstract = {Sodium 2,3-dimercapto-1-propane sulfonate (DMPS) has been used to treat acute arsenic poisoning. Presumably DMPS functions by chelating some arsenic species to increase the excretion of arsenic from the body. However, the excreted complex of DMPS with arsenic has not been detected. Here we describe a DMPS complex with monomethylarsonous acid (MMA(III)), a key trivalent arsenic in the arsenic methylation process, and show the presence of the DMPS-MMA(III) complex in human urine after the administration of DMPS. The DMPS-MMA(III) complex was characterized using electrospray tandem mass spectrometry and determined by using HPLC separation with hydride generation atomic fluorescence detection (HGAFD). The DMPS-MMAIII complex did not form a volatile hydride with borohydride treatment. On-line digestion with 0.1 M sodium hydroxide following HPLC separation decomposed the DMPS-MMA(III) complex and allowed for the subsequent quantification by hydride generation atomic fluorescence. Arsenite (As-III), arsenate (As-V), monomethylarsonic, acid (MMA(V)), dimethylarsinic acid (DMA(V)), MMA(III), and DMPS-MMA(III) complex were analyzed in urine samples from human subjects collected after the ingestion of 300 mg of DMPS. The administration of DMPS resulted in a decrease of the DMA(V) concentration and an increase of the MMA(V) concentration excreted in the urine, confirming the previous results. The finding of the DMPS-MMA(III) complex in human urine after DMPS treatment provides an explanation for the inhibition of arsenic methylation by DMPS. Because MMA(III) is the substrate for the biomethylation of arsenic from MMA(V) to DMA(V), the formation of DMPS-MMA(III) complex would reduce the availability of MMA(III) for the subsequent biomethylation.}, keywords = {ARSENICALS, CHALLENGE TEST, DRINKING-WATER, ENZYMATIC, GLUTATHIONE-REDUCTASE, HUMAN HEPATOCYTES, IN-VITRO INHIBITION, LIVER, METHYLATED, METHYLATION, MONOMETHYLARSONOUS ACID MMA(III), RABBIT, THIOREDOXIN REDUCTASE}, isbn = {0893-228X}, url = {://000178807800016}, author = {Gong, Z. and Jiang, G. F. and Cullen, W. R. and Aposhian, H. V. and Le, X. C.} } @article {5083, title = {Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid}, journal = {Journal of Analytical Atomic Spectrometry}, volume = {16}, number = {12}, year = {2001}, note = {ISI Document Delivery No.: 498MYTimes Cited: 95Cited Reference Count: 52}, pages = {1409-1413}, type = {Article}, abstract = {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.}, keywords = {ATOMIC FLUORESCENCE DETECTION, BLACKFOOT DISEASE, chemical, DRINKING-WATER, ENZYMATIC, GLUTATHIONE-REDUCTASE, HUMAN HEPATOCYTES, HUMAN URINE, LIQUID-CHROMATOGRAPHY, METHYLATION, RABBIT LIVER, SPECIATION}, isbn = {0267-9477}, url = {://000172516100011}, author = {Gong, Z. L. and Lu, X. F. and Cullen, W. R. and Le, X. C.} }