Application of micellar and microemulsion electrokinetic chromatography for characterization of gallium(III) complexes of pharmaceutical significance.
CE with conventional UV detection has recently been shown as a highly effective means to assaying cytotoxic gallium(III)-based compounds with regard to desirable drug-like properties such as the stability and binding to serum proteins. In this extension of that work, different CE techniques are used to further characterize a given set of gallium coordination compounds with established antiproliferating efficacy. Using free-zone CE mode, the electrophoretic profiles of complexes are recorded in order to assess their actual charge state under physiological buffer conditions. Micellar and microemulsion electrokinetic chromatographic techniques are tested as tools for the rapid estimation of the n-octanol-water partition coefficient (log P) that provides a rationale estimate of a drug's ability to cross biological membranes. A range of electrolyte buffer systems with varying (both in the nature and concentration) organic modifiers are examined to evaluate their effect on the relationship between experimental or calculated log P and the retention factors of compounds (log k'). Both methods were found to be better applicable for neutral than for cationic Ga complexes, the microemulsion mode demonstrating superior lipophilicity estimations as well as statistically meaningful log P versus log k' correlations when all the complexes were included in one regression set.
Timerbaev
Andrei R
AR
Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, Moscow, Russia. andrei.timerbaev@univie.ac.at
Vasylenko
Oksana O
OO
Foteeva
Lidia S
LS
Rudnev
Alexander V
AV
Semenova
Olga
O
Keppler
Bernhard K
BK
D000970:Antineoplastic Agents / Q000737:chemistry; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D004655:Emulsions; D005708:Gallium / Q000737:chemistry*
D000970:Antineoplastic Agents; D004655:Emulsions; D005708:Gallium