title: High-throughput method for lipophilicity measurement.
abstract: A high-throughput method has been developed for lipophilicity measurement. It measures the partition coefficient of a solute between a polymer phase and an aqueous phase (Ppw) in a 96-well format. The polymer is plasticized poly(vinyl chloride) (PVC), which is widely used as a material for clinical containers and ion-selective electrodes. The composition is 2:1 (w/w) dioctyl sebacate and PVC. With six repeats, log Ppw values of 15 solutes have been determined in one 96-well microplate in 4 h. A linear relationship between log Ppw and log Pow (octanol-water partition coefficient) values exists with a correlation coefficient of 0.979. The slope and intercept of the log Ppw vs log Pow plot are statistically indistinguishable from 1 and 0, respectively. Similar to the HPLC method, by using the correlation line as a calibration curve, the measured log Ppw values can be used to predict log Pow. This protocol is faster than the HPLC method. Moreover, it is straightforward to extend the protocol to the determination of the distribution coefficient and pKa of charged solutes. We show that the log Ppw of the neutral form of racemic econazole is 4.83(+/-0.06), for the cationic form (presumably as a dihydrogen phosphate ion pair) 1.68(+/-0.04), and the pKa is 6.15(+/-0.04). This method has great flexibility as well and is potentially fully automated.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Weber
mesh_terms: D001331:Automation; D002412:Cations; D057927:Hydrophobic and Hydrophilic Interactions; D008722:Methods; D011108:Polymers; D011143:Polyvinyl Chloride; D012995:Solubility; D014867:Water
chemical_list: D002412:Cations; D011108:Polymers; D014867:Water; D011143:Polyvinyl Chloride