Ultratraces Analyses Aquitaine, Hélioparc Pau-Pyrénées, 2, avenue du Président Angot, 64053 Pau Cedex 9, France.
Anal Bioanal Chem. 2012 Dec;404(10):2939-48. doi: 10.1007/s00216-012-6427-3. Epub 2012 Oct 7.
Meglumine antimonate is the active of Glucantime® used for the treatment of leishmaniasis, a tropical disease caused by parasitic protozoa, and it is estimated that 12 million people worldwide are affected. This drug mainly contains Sb(V) under the form of an organic complex with N-methylglucamine (NMG). During the synthesis of this molecule, traces of Sb(III) may be present, also probably complexed. Due to the fact that Sb(III) is considered more toxic than Sb(V), it is important to evaluate the Sb(III) concentration in the drug samples. In the literature, very different concentrations for residual concentrations of Sb(III) in the drug ampoules are found. Therefore, to have a true insight of antimony speciation, two independent analytical methods were developed in this work. We used an anion exchange method coupled with inductively coupled plasma mass spectrometry (ICP-MS) which was cross-referenced with an electrochemistry method (differential pulse polarography (DPP)) that could be used for routine analysis on the production site. To obtain Sb species in detectable forms, the complexes between Sb species and NMG need to be broken. This was obtained by diluting samples in hydrochloric acid in deaerated conditions to avoid Sb redox reactions. For the two analytical methods, the HCl concentration was optimized to obtain simultaneously a complete destruction of the complexes as well as limited redox reactions for Sb(V) and Sb(III) released species. For high-performance liquid chromatography (HPLC)-ICP-MS, a dilution with 5 M HCl gives the better results. The side reaction is an oxidation of Sb(III) which can be limited by the removal of oxygen. When DPP is used, the major problem is the reduction of Sb(V) which is present in high amount in the samples. Working with 0.6 M HCl allows this problem to be minimized. When applied to different lots of Glucantime®, Sb(III) concentration values are in good agreement for the two analytical methods, with, for HPLC-ICP-MS, the advantage of the simultaneous detection of both Sb redox species.
葡甲胺锑酸盐是葡聚糖锑的有效成分，用于治疗利什曼病，这是一种由寄生虫原生动物引起的热带疾病，据估计，全球有 1200 万人受到影响。这种药物主要含有 Sb(V)，以与 N-甲基葡糖胺（NMG）形成的有机络合物形式存在。在这种分子的合成过程中，可能存在 Sb(III)的痕迹，也可能与之络合。由于 Sb(III)被认为比 Sb(V)毒性更大，因此评估药物样品中的 Sb(III)浓度非常重要。在文献中，发现药物安瓿中残留 Sb(III)浓度的差异非常大。因此，为了真正了解锑的形态，本工作开发了两种独立的分析方法。我们使用阴离子交换法结合电感耦合等离子体质谱法（ICP-MS），并与电化学法（差示脉冲极谱法（DPP））进行了交叉参考，后者可用于生产现场的常规分析。为了获得可检测形式的 Sb 物种，需要打破 Sb 物种与 NMG 之间的络合物。这是通过在脱氧条件下将样品稀释在盐酸中实现的，以避免 Sb 的氧化还原反应。对于这两种分析方法，优化了 HCl 浓度，以同时获得完全破坏络合物以及 Sb(V)和 Sb(III)释放物种的有限氧化还原反应。对于高效液相色谱（HPLC）-ICP-MS，用 5 M HCl 稀释可获得更好的结果。副反应是 Sb(III)的氧化，可通过去除氧气来限制。当使用 DPP 时，主要问题是存在大量样品中的 Sb(V)的还原。使用 0.6 M HCl 可以最小化这个问题。应用于不同批次的葡聚糖锑，两种分析方法得到的 Sb(III)浓度值非常吻合，对于 HPLC-ICP-MS 来说，其优势在于同时检测两种 Sb 氧化还原物种。
