title: Determination of multiple human arsenic metabolites employing high performance liquid chromatography inductively coupled plasma mass spectrometry.
abstract: During the metabolism of different arsenic-containing compounds in human, a variety of metabolites are produced with significantly varying toxicities. Currently available analytical methods can only detect a limited number of human metabolites in biological samples during one run due to their diverse characteristics. In addition, co-elution of species is often unnoticeable with most detection techniques leading to inaccurate metabolic profiles and assessment of toxicity. A high performance liquid chromatography inductively coupled mass spectrometry (HPLC-ICP-MS) method was developed that can identify thirteen common arsenic metabolites possibly present in human with special attention dedicated to thiolated or thiol conjugated arsenicals. The thirteen species included in this study are arsenite (As(III)), arsino-glutathione (As(GS)3), arsenate (As(V)), monomethylarsonous acid (MMA(III)), monomethylarsino-glutathione (MMA(III)(GS) 2), monomethylarsonic acid (MMA(V)), dimethylarsinous acid (DMA(III) (from DMA(III)I)), S-(dimethylarsinic)cysteine (DMA(III) (Cys)), dimethylarsino-glutathione (DMA(III)(GS)), dimethylarsinic acid (DMA(V)), dimethylmonothioarsinic acid (DMMTA(V)), dimethyldithioarsinic acid (DMDTA(V)), dimethylarsinothioyl glutathione (DMMTA(V)(GS)). The developed method was applied for the analysis of cancer cells that were incubated with darinaparsin (DMA(III)(GS)), a novel chemotherapeutic agent for refractory malignancies, and the arsenic metabolic profile obtained was compared to results using a previously developed method. This method provides a useful analytical tool which is much needed in unequivocally identifying the arsenicals formed during the metabolism of environmental arsenic exposure or therapeutic arsenic administration.
authors.affiliation: Department of Chemistry & Biochemistry, FL International University, 11200 SW 8th St., Miami, FL 33199, United States.
authors.forename: Szabina
authors.initials: S
authors.lastname: Stice
authors.affiliation: Department of Chemistry & Biochemistry, FL International University, 11200 SW 8th St., Miami, FL 33199, United States.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States.
authors.forename: Shannon
authors.initials: S
authors.lastname: Matulis
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Boise
authors.affiliation: Department of Chemistry & Biochemistry, FL International University, 11200 SW 8th St., Miami, FL 33199, United States; Southeast Environmental Research Center, FL International University, Miami, FL 33199, United States. Electronic address: cai@fiu.edu.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
mesh_terms: D001152:Arsenicals / Q000032:analysis* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D006801:Humans; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism; D013455:Sulfur / Q000032:analysis / Q000378:metabolism
chemical_list: D001152:Arsenicals; D013455:Sulfur; C515055:darinaparsin; D005978:Glutathione
keywords: Arsenic metabolism in humans; Arsenic speciation; Dimethylarsinous glutathione; High performance liquid chromatography inductively coupled mass spectrometry (HPLC-ICP-MS)