Speciation of arsenic in urine following intravenous administration of arsthinol in mice

• Published in: European journal of drug metabolism and pharmacokinetics Vol. 35; no. 1-2; pp. 59 - 65
• Main Authors: Ajana, Imane, Astier, Alain, Gibaud, Stéphane
• Format: Journal Article
• Language: English
• Published: Paris Springer-Verlag 01-09-2010; Médecine & hygiène; Springer
• Subjects: Animals; Antineoplastic Agents; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - urine; Arsenic; Arsenic - pharmacokinetics; Arsenicals; Arsenicals - pharmacokinetics; Arsenicals - urine; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid; Female; Human Physiology; Life Sciences; Mass Spectrometry; Medical Biochemistry; Medical sciences; Mice; Original Paper; Oxides; Oxides - urine; Pharmaceutical sciences; Pharmaceutical Sciences/Technology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Urine; Urine - chemistry; Urine samples; LC-MS; Arsenic; Speciation; Arsthinol; Urine; Biological fluid; Intravenous administration; Rodentia; HPLC chromatography; Exploration; Antiprotozoal agent; Carcinogen; Vertebrata; Mammalia; Mouse; Animal; Parasiticide; Mass spectrometry; Arsenic Organic compounds
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-010-0009-6

Recent investigations have shown that arsthinol, a trivalent organoarsenic compound (dithiarsolane), has been active in vitro on leukemia cell lines and offers a better therapeutic index than arsenic trioxide, as estimated by the ratio LD
50
/IC
50
. To complete our understanding of its urinary excretion, a sensitive method using liquid chromatography coupled with mass spectrometry (LC-MS) was used. Mice were injected intravenously with a single dose of arsthinol at 0.2 mmol/kg of body weight. The amount of total arsenic in tissues and body fluids was determined by a colorimetric method and urine metabolites were analyzed on a C18 Acclaim PepMap 100 Å column by LC-MS. Our results showed that only three arsenic species (acetarsol, acetarsol oxide and arsthinol) were detected in the first 24-h urine. Overall, this study confirms that the hydrolysis of dithiarsolanes to arsenoxides (i.e. acetarsol oxide) can be followed by an oxidation in arsonic acids (i.e. acetarsol). All these compounds are excreted in the urine.