Electrophoresis, Vol.26, No.4-5, 878-884, 2005
Analysis of anticancer platinum(II)-complexes by microemulsion electrokinetic chromatography: Separation of diastereomers and estimation of octanol-water partition coefficients
Microemulsion electrokinetic chromatography (MEEKC) was applied for the separation and lipophilicity estimation of oxaliplatin and eight novel anticancer oxaliplatin derivatives. Solubility and permeability have to be balanced in modern drug development, and the octanol-water partition coefficient (log P) still represents one of the most useful quantifiable parameters providing a reasonable estimation of a drug's lipophilicity. Therefore, the capacity factors from MEEKC were correlated to log P values derived by the traditional shake flask method. The IVIEEKC method was accomplished using a microemulsion of heptane/sodium dodecyl sulfate (SDS)/butanol in phosphate buffer at pH 7.4 and 37degreesC with all analytes being in a neutral state during the run. This experimental setup allowed a baseline separation of all platinum complexes within 11 min. Remarkably, beside the very good resolution and precision of the measurements, separation of diastereomers of the complexes and quantification of the diastereomeric ratios could be achieved. Correlating the capacity factors with the corresponding log P values resulted in a linear dependency with a correlation factor of r = 0.9935. Consequently, the applied IVIEEKC method was found to be a highly valuable technique not only for the separation of platinum complexes but as well for the estimation of the octanol-water partition coefficient with many advantages in comparison to other methods.