Carrier Mediated Distribution System (CAMDIS): A new approach for the measurement of octanol/water distribution coefficients

Here we present a miniaturized assay, referred to as Carrier-Mediated Distribution System (CAMDIS) for fast and reliable measurement of octanol/water distribution coefficients, log Doct  . By introducing a filter support for octanol, phase separation from water is facilitated and the tendency of emulsion formation (emulsification) at the interface is reduced. A guideline for the best practice of CAMDIS is given, describing a strategy to manage drug adsorption at the filter-supported octanol/buffer interface. We validated the assay on a set of 52 structurally diverse drugs with known shake flask logDoctlogDoct values. Excellent agreement with literature data (r2 = 0.996, standard error of estimate, SEE = 0.111), high reproducibility (standard deviation, SD < 0.1 log Doct units), minimal sample consumption (10 μL of 100 μM DMSO stock solution) and a broad analytical range (log Doct range = −0.5 to 4.2) make CAMDIS a valuable tool for the high-throughput assessment of log Doct.

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