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An Increased Throughput Method for the Determination of Partition Coefficients

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Abstract

Purpose. To present an increased throughput automated shake-flask method for 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-well plate technology and a robotic liquid handler has been used for sample preparation. A custom programmed Gilson auto- sampler samples the organic and aqueous phases directly from the plate, circumventing the need for any manual separation. Analyses are performed by reverse phase high performance liquid chromatography (RP-HPLC). Generic fast gradient RP-HPLC conditions are used to eliminate chromatographic method development time and reduce analysis 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 method are discussed. The use of this methodology provides a means to rapidly assess log D values for large compound arrays.

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Hitzel, L., Watt, A.P. & Locker, K.L. An Increased Throughput Method for the Determination of Partition Coefficients. Pharm Res 17, 1389–1395 (2000). https://doi.org/10.1023/A:1007546905874

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  • DOI: https://doi.org/10.1023/A:1007546905874

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