An increased throughput method for the determination of partition coefficients

Purpose. To present an increased throughput automated shake-flask method fu r the direct determination of the partition coefficients of solutes between octan-1-ol and buffer. Method. The traditional shake-flask method has been transferred onto 96-wel l plate technology and a robotic liquid handler has been used for sample pr eparation. A custom programmed Gilson autosampler samples the organic and a queous phases directly from the plate, circumventing the need for any manua l separation. Analyses are performed by reverse phase high performance liqu id chromatography (RP-HPLC). Generic fast gradient RP-NPLC conditions are u sed to eliminate chromatographic method development time and reduce analysi s time. Results. A full validation of the automated method is presented for a range of compounds with log D values between -2 and 4. Conclusions. The advantages and limitations of this direct measurement meth od are discussed. The use of this methodology provides a means to rapidly a ssess log D values for large compound arrays.