Abstract

Purpose: To develop a rapid screening method for the determination of the octanol-water partition coefficients (log P) of drugs by microemulsion electrokinetic chromatography (MEEKC). Methods: Two microemulsion systems consisting of 1.6% sodium dodecyl sulfate, 5.0% butanol, and 0.4% heptane in 20 mmol/l borate buffer (pH 10.1) or 10 mmol/l phosphate buffer (pH 12.0) (w/w), were prepared to determine the capacity factors (log k_MEEKC) of a series of neutral and basic compounds and three programs from ACD/Labs, Marvin, Tsar, were used to calculate the log P (Clog P). Then, two sets of log k_MEEKC values and three sets of Clog P values were correlated with the experimental log P (Elog P) values obtained from the literature. Results: The correlation coefficients between
Elog P and log k_MEEKC (pH 10.1), log k_MEEKC (pH 12.0), Clog P (ACD/Labs), Clog P (Marvin), Clog P (Tsar) values were 0.972, 0.980,
0.992, 0.898, 0.881 for the small organic compounds (SOCs) set and 0.888, 0.877, 0.786, 0.738, 0.777 for the drug set. A linear equation,
log P=1.5962 log k_MEEKC+1.1466 (R²=0.981), was developed for the determination of the log P values of drugs. Conclusion: The log k_MEEKC values of SOCs and drugs exhibited different correlations with Elog P. The log P values of SOCs can be predicted accurately by the ACD/Labs program, while the log P values of drugs were predicted better by MEEKC methods.


Keywords:  Microemulsion electrokinetic chromatography   Octanol-water partition coefficient   Capacity factor