Introduction Arsenic trioxide (ATO) is a well-known toxic metalloid that has been used for treating various diseases such as ulcers, the plague, and malaria for more than two millennia ( 1 daily until CR ( Increasing evidence from clinical and laboratory studies demonstrates that how ATO exerts its pharmacological activities and initiates the toxicological process mainly depends on the generation of various active metabolic intermediates ( III , the hydrolyzed form of ATO) is subjected to sequential reduction and oxidative methylation reactions in the blood to form arsenate (As V ), monomethylated arsenic (MMA), and dimethylated arsenic (DMA) ( III , DMA III ), are more toxic than inorganic arsenic (iAs, including As III and As V ) ( V , DMA V ) are the predominant arsenic methylated metabolites in urine, which are considered a tumor promoter and significantly associated with adverse health effects ( In the present study, high-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) was applied to determine the content of various arsenic metabolites (As III , As V , MMA, DMA) in plasma to elucidate the pharmacokinetic characteristics of oral ATO
doi: 10.1016/j.ejphar.2009.04.022 28 D'AgostinoG.RussoR.AvaglianoC.CristianoC.MeliR.CalignanoA
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