Determination of arsenic metabolic complex excreted in human urine after administration of sodium 2,3-dimercapto-1-propane sulfonate.
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-MMA(III) 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.
Gong
Zhilong
Z
Department of Public Health Sciences, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
Jiang
Guifeng
G
Cullen
William R
WR
Aposhian
H Vasken
HV
Le
X Chris
XC
D001151:Arsenic / Q000378:metabolism* / Q000652:urine; D001152:Arsenicals / Q000032:analysis / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004785:Environmental Pollutants / Q000378:metabolism* / Q000652:urine; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization; D013723:Teratogens / Q000032:analysis / Q000737:chemistry*; D014494:Unithiol / Q000737:chemistry / Q000494:pharmacology*
D001152:Arsenicals; D002614:Chelating Agents; D004785:Environmental Pollutants; D013723:Teratogens; D014494:Unithiol; C020300:monomethylarsonic acid; D001151:Arsenic