New insights into the chemical structure and composition of the pentavalent antimonial drugs, meglumine antimonate and sodium stibogluconate

The chemical structures of the pentavalent antimonial drugs, meglumine antimonate (MA) and sodium stibogluconate (SSG), were re-evaluated using electrospray ionization mass spectrometry (ESI-MS) and osmolarity measurements. Both MA and SSG were found to contain 1:1, 1:2, 2:2 and 2:3 SbV-ligand complexes. ESI-MS analysis of MA showed negatively-charged 1:1 (m/z 364) and 2:2 (m/z 765) SbV–meglumine complexes, supporting the predominance of zwitterionic species in solution. Our data are consistent with a structure for the 1:2 SbV–meglumine, which differs from that previously postulated, with two positively-charged amino groups and one negatively-charged antimonate group. Instead of the commonly hypothesized structure for SSG, in which two Sb atoms are linked by an oxygen, an alternative structure is proposed, based on the ability of SbV–gluconate complexes to polymerize. MA (or SSG) in concentrated aqueous solutions, such as of MA (or SSG) in its commercial form, is expected to consist mainly of a mixture of 2:2, 2:3 and 2:1 SbV-ligand complexes, as suggested by the 2:1 Sb-to-particle ratio found by osmometry. 1:1 SbV-ligand complexes in MA and SSG are expected to play an important pharmacological role, as suggested by the slow increase of osmolarity of MA solution upon dilution at 37 °C (half-time of 20 min).