title: Dimethylthioarsenicals as arsenic metabolites and their chemical preparations.
abstract: Two unidentified arsenic metabolites were detected in the liver of rats on a gel filtration column by HPLC inductively coupled argon plasma mass spectrometry after an injection of dimethylarsinic (DMA(V)), dimethylarsinous (DMA(III)), monomethylarsonic (MMA(V)), or monomethylarsonous (MMA(III)) acid. The same arsenicals were also produced in vitro by incubation of DMA(III) in the liver supernatant but not by DMA(V). The two arsenic metabolites eluted at the same retention times as those of the two arsenicals prepared by reaction of DMA(V) with either thiosulfate plus disulfite or hydrogen sulfide or sodium sulfide plus sulfuric acid. The faster and slower eluting products on a gel filtration column were assigned as dimethyldithioarsinic acid (dimethylarsinodithioic acid) (DMTA(V)) and dimethylthioarsinous acid (DMTA(III)) from mass spectrometric data at m/z = 170 and 138 by electrospray ionization mass spectrometry with negative and positive ion modes, respectively. They were prepared selectively by reacting DMA(V) with hydrogen sulfide or sodium sulfide plus sulfuric acid under different reaction conditions. DMA(III) but not DMA(V) was transformed to DMTA(III) and DMTA(V) in the presence of sodium sulfide in vitro, suggesting that DMA(V) is reduced to DMA(III) with hydrogen sulfide, thiolated to DMTA(III), and then further thiolated oxidatively to DMTA(V). Metabolically, it is assumed that DMA(III) is transformed to DMTA(III) in the presence of sulfide ions, and then, DMTA(III) is oxidatively thiolated to DMTA(V). As the chemical species produced by reduction with the Reay and Asher method are DMTA(III) and DMTA(V), and different from DMA(III), the studies carried out with DMA(III) with the Reay and Asher method have to be reexamined.
authors.affiliation: Department of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. ktsuzuki@p.chiba-u.ac.jp
authors.forename: Kazuo T
authors.initials: KT
authors.lastname: Suzuki
authors.forename: Badal K
authors.initials: BK
authors.lastname: Mandal
authors.forename: Akio
authors.initials: A
authors.lastname: Katagiri
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kawakami
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Ogra
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sei
authors.forename: Kenzo
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Kazunori
authors.initials: K
authors.lastname: Anzai
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ohmichi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takayama
authors.forename: Noriro
authors.initials: N
authors.lastname: Aimi
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001152:Arsenicals