Speciation of antimony in injectable drugs used for leishmaniasis treatment (Glucantime®) by HPLC-ICP-MS and DPP

Abstract

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.

Atomic spectrometry update: review of advances in the analysis of metals, chemicals and materials

“…As Sb(III) is more toxic than Sb(V), the determination of these Sb species is, therefore, required. The concentrations of Sb(III) are difficult to determine accurately and Seby et al 125 have developed two independent procedures for the determination of Sb species. In the rst procedure, an anion exchange IC separation was coupled with ICP-MS.…”

Atomic spectrometry updates. Review of advances in elemental speciation

“…Since Sb III is considered more toxic than Sb V , it is important to evaluate the Sb III concentration in the drug samples. The literature reports very different concentrations for residual concentrations of Sb III in drug ampoules, and so Seby et al 68 have compared an anion exchange method coupled to ICP-MS 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.…”

Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS

“…High performance liquid chromatography (HPLC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) is a widely used technique in elemental speciation of compounds such as arsenic, chromium, mercury, selenium and antimony [24,25,26,27,28]. Arsenic species in human urine have been analyzed; although urine is a commonly accepted indicator of arsenic exposure [29,30,31], arsenic in blood may indicate exposure to recent arsenic-containing drugs.…”