A microscale hplc method for the evaluation of octanol-water partition coefficients in a series of new 2-amino-2-oxazolines

A rapid and simple microscale method for the determination of octanol-water partition coefficients has been developed and evaluated for a series of twenty-six bioactive 2-amino-2-oxazolines. Solutes were equilibrated between n-octanol and water by using the shake-flask approach in a single partitioning. The concentration of each compound was measured in the aqueous phase before and after partitioning directly by RP-HPLC, and the peak areas ratio was used to calculate the partition coefficient log P. Log P values ranging from -0.22 to 3.69 have been determined with a precision better than +/- 0.06 log unit. They were compared with the measured shake-flask octanol-water partition coefficient and with the calculated incremental Clog P values. The linear regression analyses between these lipophilic parameters show significant correlations, allowing validation of this chromatographic approach for the log P determination.