Skip to main content
SpringerLink
Log in

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

  • Original Paper
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

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 LD50/IC50. 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Ajana I et al (2009) Arsthinol nanosuspensions: pharmacokinetics and antileukemic activity on NB4 promyelocytic leukemia cells. J Pharm Pharmacol 61:1295–1301

    Article  CAS  PubMed  Google Scholar 

  • Ben Zirar S et al (2007) Pharmacokinetics and tissue distribution of the antileukaemic organoarsenicals arsthinol and melarsoprol in mice. J Organomet Chem 692:1348–1352

    Article  CAS  Google Scholar 

  • Berger BJ, Fairlamb AH (1994) Properties of melarsamine hydrochloride (Cymelarsan) in aqueous solution. Antimicrob Agents Chemother 38:1298–1302

    CAS  PubMed  Google Scholar 

  • Cristau B et al (1972) Voies et cinétiques d’élimination de l’arsenic chez le rat après administration de médicaments organoarséniés––II. Etude du mélarsoprol et du mélarsonyl potassique. Med Trop (Mars) 32:275–283

    CAS  Google Scholar 

  • Cristau B et al (1973) Elimination biliaire chez le rat de quelques médicaments organoarseniés. J Pharmacol 4:199–207

    CAS  Google Scholar 

  • Cristau B et al (1975) Voies et cinétiques d’excrétion de l’arsenic chez le Cobaye après injection de divers médicaments organo-arséniés. Ann Pharm Fr 33:577–589

    CAS  PubMed  Google Scholar 

  • Devesa V et al (2004) Comprehensive analysis of arsenic metabolites by pH-specific hydride generation atomic absorption spectrometry. J Anal At Spectrom 19:1460–1467

    Article  CAS  Google Scholar 

  • Elliot SC, Loper BR (1974) Improved absorption tube for arsenic determinations. Anal Chem 46:2256–2257

    Article  Google Scholar 

  • Forkner C, Scott T (1931) Arsenic as a therapeutic agent in chronic myelogenous leukemia. J Am Med Assoc 97:3–5

    Google Scholar 

  • Gibaud S et al (2006) (2-Phenyl-[1, 3, 2] dithiarsolan-4-yl)-methanol derivatives show in vitro antileukemic activity. J Organomet Chem 691:1081–1084

    Article  CAS  Google Scholar 

  • Goldman L et al (1956) Arsthinol (Balarsen) in dermatology. Dermatologica 113:369–374

    Article  CAS  PubMed  Google Scholar 

  • Gregus Z, Gyurasics A (2000) Role of glutathione in the biliary excretion of the arsenical drugs trimelarsan and melarsoprol. Biochem Pharmacol 59:1375–1385

    Article  CAS  PubMed  Google Scholar 

  • Harrison R (2002) Structure and function of xanthine oxidoreductase: where are we now? Free Radic Biol Med 33:774–797

    Article  CAS  PubMed  Google Scholar 

  • Hughes MF et al (2003) Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate. Toxicol Appl Pharmacol 191:202–210

    Article  CAS  PubMed  Google Scholar 

  • Most H et al (1954) Arsthinol (Balarsen), a new trivalent arsenical for the treatment of intestinal amebiasis and other intestinal protozoa. Am J Trop Med Hyg 3:262–265

    CAS  PubMed  Google Scholar 

  • Pick E, Keisari Y (1980) A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Methods 38:161–170

    Article  CAS  PubMed  Google Scholar 

  • Shen ZX et al (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 89:3354–3360

    CAS  PubMed  Google Scholar 

  • Waxman S, Anderson KC (2001) History of the development of arsenic derivatives in cancer therapy. Oncologist 6:3–10

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the « Service commun de spectrométrie de masse » de l’Université Henri Poincaré, Faculté des Sciences et Techniques, 54 506 Vandœuvre lès Nancy.

Author information

Authors and Affiliations

  1. Pharmacie Clinique, EA 3452 « Cibles thérapeutiques, formulation et expertise pré-clinique du médicament », Université Henri Poincaré, Nancy Université, 5, rue Albert Lebrun, BP 80403, 54001, Nancy Cedex, France

    Imane Ajana, Alain Astier & Stéphane Gibaud

Authors
  1. Imane Ajana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alain Astier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stéphane Gibaud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stéphane Gibaud.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ajana, I., Astier, A. & Gibaud, S. Speciation of arsenic in urine following intravenous administration of arsthinol in mice. Eur J Drug Metab Pharmacokinet 35, 59–65 (2010). https://doi.org/10.1007/s13318-010-0009-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-010-0009-6

Keywords

Search

Navigation