Partition coefficients high-throughput

It is also quite interesting that lipid model 4.0 may be used to obtain alkane partition coefficients at high-throughput speeds, as suggested by Faller and Wohnsland [509,554], It is also interesting to note that since our Pe are corrected for membrane retention, the slope in Fig. 7.11 corresponding to the dashed line (our data) is 1.0, whereas the data not corrected for retention (solid line) show a lesser slope. This may not matter if the objective is to obtain alkane-water log Kp values at high speeds. 

The partition coefficient logP or the distribution coefficient logD between water and n-octanol are determined traditionally by the shake flask method (see chapter about physicochemical parameters). The shake flask method is a rather labour intensive method and not suited for high throughput analysis needed in pharmaceutical research. 

Reversed phase high-performance liquid chromatography (RP-HPLC) is an indirect, rapid, and high throughput method for the determination of partition coefficients. In HPLC, the most frequently used retention factor, k, is defined as ... 

There are obviously many methods to determine partition coefficients, directly and indirectly. Many of the newer high throughput procedures provide a rapid, easy to use, reproducible cost-effective way to assay the hydrophobicity of large numbers of diverse compounds however, there are a few caveats. In some cases, the range of partition coefficients that has been validated is limited. In HT screens with 1-octanol, a 10,000 to 1 distribution ratio would be difficult to access and assess thus the reliability of log Poet values at the ends of the spectrum (< 3 or >5) would be much lower than shake-flask values when dealing with minute volumes such as those present in a 96-well plate. 

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