Accurate, wide-range, automated, high-performance liquid chromatographic method for the estimation of octanol/water partition coefficients I: Effect of chromatographic conditions and procedure variables on accuracy and reproducibility of the method.

A high-performance liquid-chromatographic (HPLC) procedure is reported for estimation of the logarithm of the octanol/water partition coefficient, log P(o/w). This automated log P(o/w) measurement (ALPM) circumvents many inherent difficulties with the shake-flask method, yet gives high reproducibility and excellent overall correlation with shake-flask results. Partition coefficients for numerous structurally diverse chemicals, ranging from approximately 0 to approximately 8 log P(o/w) units, can be determined; however, values for zwitterionic compounds cannot be obtained. Additional advantages of ALPM include lower cost and greater safety when compared with other HPLC or shake-flask procedures. Chromatographic conditions (i.e., flow rate and temperature) and variables (i.e., column length and solvent composition) affecting this method are discussed in detail. ALPM may also find application in quality control of HPLC columns, qualitative-quantitative analysis, and in computer-controlled method development and analysis.