School of Environmental Sciences, University of Liverpool, 4 Brownlow Street, Liverpool L69 3GP, UK.
Anal Bioanal Chem. 2013 Jun;405(15):5201-14. doi: 10.1007/s00216-013-6947-5. Epub 2013 Apr 24.
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 (<6%, N = 100), precise (5%, N = 5) and robust (same electrode used for weeks) at all pH values. In diluted solutions of Glucantime, Sb(III) levels were strongly dependent both on pH and ionic strength. At pH < 3, Sb(III) is oxidized with oxidation rates that increase as pH is decreased. At high pH, Sb(III) forms electro-inactive complexes. Highest Sb(III) levels were detected at pH ~3 and at low ionic strength. The presence of several Sb(III) and Sb(V) species was demonstrated by different reduction waves obtained by stripping scanned voltammetry. As an implication of these unexpectedly high Sb(III) concentrations, an alternative model can be proposed for the mode of action of pentavalent antimonials against leishmaniasis, in which antimony complexes may act as molecular carrier of Sb(III) and release it specifically in the acidic intracellular compartment where the Leishmania parasites reside.
葡萄糖酸锑，一种五价锑药物，通常用于治疗利什曼病，但残留的三价锑（Sb(III)）被认为是导致患者出现毒副作用的原因。许多分析研究都集中在测定葡萄糖酸锑中的 Sb(III)浓度上，但没有达成共识：结果跨度超过 3 个数量级。在这项研究中，我们提出了一种详细的新分析方法，表明：(1) Sb(III)水平远高于先前报道的水平，占总 Sb 的 30%以上；(2) 在酸性条件下测定 Sb(III)浓度受到快速氧化速率的阻碍。这后一点解释了以前报道的葡萄糖酸锑中 Sb(III)浓度的巨大差异。这里在振动金微丝电极上通过溶出伏安法进行了测量，能够在酸性、中性或碱性条件下测量 Sb(III)。所开发的方法在所有 pH 值下都具有高灵敏度（例如，在 pH 4.5 下 120 秒沉积时检测限为 19 pM）、稳定（<6%，N=100）、精确（5%，N=5）和稳健（同一电极可使用数周）。在葡萄糖酸锑的稀释溶液中，Sb(III)水平既依赖于 pH 值又依赖于离子强度。在 pH<3 时，Sb(III)被氧化，氧化速率随 pH 值降低而增加。在高 pH 值下，Sb(III)形成非电活性络合物。在 pH~3 和低离子强度下检测到最高的 Sb(III)水平。通过溶出扫描伏安法获得的不同还原波证明了几种 Sb(III)和 Sb(V)物种的存在。由于这些出乎意料的高 Sb(III)浓度的存在，可以提出一种五价锑对利什曼病作用模式的替代模型，其中锑络合物可以作为 Sb(III)的分子载体，并将其特异性释放到利什曼原虫所在的酸性细胞内环境中。
