Unexpectedly high levels of antimony (III) in the pentavalent antimonial drug Glucantime: insights from a new voltammetr
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RESEARCH PAPER
Unexpectedly high levels of antimony (III) in the pentavalent antimonial drug Glucantime: insights from a new voltammetric approach Pascal Salaün & Frédéric Frézard
Received: 19 December 2012 / Revised: 20 March 2013 / Accepted: 25 March 2013 / Published online: 24 April 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Glucantime, a pentavalent antimonial drug, is commonly used for the treatment of leishmaniasis but the presence of residual trivalent antimony, Sb(III), is thought to be responsible for toxic side-effects observed in patients. Numerous analytical studies have focused on determining Sb(III) concentrations in Glucantime but without reaching a consensus: results span over 3 orders of magnitude. In this study, we present a detailed new analytical approach showing that: (1) Sb(III) levels are much higher than previously reported and represent more than 30 % of total Sb; (2) determination of Sb(III) concentrations in acidic conditions is hampered by fast oxidation rates. This latter point explains the large variations in previously reported results of Sb(III) concentrations in Glucantime. Measurements were made here at a vibrated gold microwire electrode by stripping voltammetry enabling measurement of Sb(III) in acidic, neutral or alkaline conditions. The developed methods are sensitive (e.g., detection limits of 19 pM for 120 s deposition at pH 4.5), stable ( 3.5 (Fig. 9) decreased significantly showing that an increase in pH strongly modifies the chemical distribution of Sb(III) with formation of electro-inactive stable complexes. Sb total determination Total Sb was determined only in MA1 and was found at 83.5±3.5 mg mL−1, in general agreement with concentrations reported in other studies (Table 2).
Sb(III) and Sb(V) levels in Glucantime &
Sb(III) determination The concentration of Sb(III) was determined by standard additions either in acetate, phosphate, hydroxide or chlorhydric acid. The experiment time was kept to a minimum with short SWASV scans (5–10 s deposition at −0.6 V, 1 s desorption at −0.8 or −1.2 V) and short conditioning step in between (1 s at −2.5 V, 2-5 s at 0.8 V) to avoid instability effects due to oxidation processes. A standard addition procedure was achieved in less than 5 min. Figure 9 displays the concentration of Sb(III) obtained in 10 mM/1 mM solutions of varying pH. Rapid loss of the Sb(III) signal prevented analysis at pH
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