Determination of multiple human arsenic metabolites employing high performance liquid chromatography inductively coupled plasma mass spectrometry

• Authors: Szabina Stice, Florida International University; Guangliang Liu, Florida International University; Shannon Matulis, Emory University; Lawrence Boise, Emory University; Yong Cai, Florida International University
• Journal Title: Journal of Chromatography B
• Volume: Volume 1009
• Publisher: Elsevier | 2016-01-15, Pages 55-65
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.jchromb.2015.12.008
• Subjects: Chemistry, Analytical; Chemistry, Biochemistry; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Biochemical Research Methods; Chemistry, Analytical; Biochemistry & Molecular Biology; Chemistry; High performance liquid chromatography inductively coupled mass spectrometry (HPLC-ICP-MS); Arsenic speciation; Arsenic metabolism in humans; Dimethylarsinous glutathione; GLUTATHIONE COMPLEXES; METHYLATED ARSENICALS; CANCER-THERAPY; TRIVALENT; EXPOSURE

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.