Pentavalent organoantimonial derivatives: two simple and efficient synthetic methods for meglumine antimonate

Abstract

Two simple and efficient procedures for the preparation of pentavalent antimony derivatives are described, using either antimony pentachloride (SbCl 5 ) or potassium hexahydroxoantimonate (KSb(OH) 6 ) as sources of antimony(V). These two new methods are evaluated for the synthesis of an important anti-leishmanial drug: meglumine antimonate. Using elemental (carbon, hydrogen, nitrogen) and thermal analysis, atomic absorption (antimony), proton NMR spectroscopy and highresolution positive-ion electrospray ionization mass spectrometry (ESI(+)-MS), products for the reaction with N-methyl-D-glucamine (NMG) using both the SbCl 5 and KSb(OH) 6 methods were characterized and found to be similar to a commercial sample of the drug. The only notable difference was observed for the ESI-MS spectrum of the KSb(OH) 6 product; it displays the same pattern of ESI-generated ions as those of both the SbCl 5 product and the commercial drug, but with significantly different abundance ratios. NMR data indicate that the NMG molecules coordinate antimony in two different fashions, which suggests either the coexistence of two different complexes or the existence of a single major complex in which two NMG molecules are coordinated with antimony in an asymmetrical geometry.

Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid

“…Two different forms of meglumine antimoniate were evaluated: the commercial form (Glu) and meglumine antimoniate (MA) synthesized from KSb(OH) 6 (17). Trace metal analysis did not show detectable levels of Pb (Ͻ2.5 g/g) or As (Ͻ1.5 g/g) in either Glu or MA.…”

“…Recently, two new synthetic processes were proposed for meglumine antimoniate (17). One of these methods used KSb(OH) 6 as a source of antimony, instead of SbCl 5 in the commercial process for Glu.…”

“…AA also was evaluated for its hepatoprotective effect during pentavalent antimonial chemotherapy and its interference with the drug antileishmanial efficacy. 6 , as previously described (17). The total antimony concentration in MA and Glu, as determined by atomic absorption spectroscopy, was ca.…”

Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

“…MA was synthesized as previously described (Demicheli et al 2003) from an equimolar mixture of N-methyl-D-glucamine and pentavalent antimony oxyhydrated in water. The resulting product contained approximately 29% of antimony by weight, as determined by plasma emission spectroscopy (ICP-OES) using a Perkin-Elmer Optima 3000 plasma emission spectrometer.…”

Oral Delivery of Meglumine Antimoniate-β-Cyclodextrin Complex for Treatment of Leishmaniasis

“…Typical spectrometer conditions were 65,536 data points, 11.19-kHz spectral width, and 10.0-s recycle time. Proton resonances were assigned using data from the literature for ␤-cyclodextrin (11) and from previous work for meglumine antimoniate (3). 1 H inversion recovery (T 1 ) peak intensity data (I[t]) were fitted to a three-parameter exponential equation:…”