title: New magnetic nano-absorbent for the determination of n-octanol/water partition coefficients.
abstract: A novel and generic miniaturization methodology for the determination of partition coefficient values of organic compounds in n-octanol/water by using magnetic nanoparticles is, for the first time, described. We have successfully designed, synthesised and characterised new colloidal stable porous silica-encapsulated magnetic nanoparticles of controlled dimensions. These nanoparticles absorbing a tiny amount of n-octanol in their porous silica over-layer are homogeneously dispersed into a bulk aqueous phase (pH 7.40) containing an organic compound prior to magnetic separation. The small size of the particles and the efficient mixing allow a rapid establishment of the partition equilibrium of the organic compound between the solid supported n-octanol nano-droplets and the bulk aqueous phase. UV-vis spectrophotometry is then applied as a quantitative method to determine the concentration of the organic compound in the aqueous phase both before and after partitioning (after magnetic separation). logD values of organic compounds of pharmaceutical interest (0.65-3.50), determined by this novel methodology, were found to be in excellent agreement with the values measured by the shake-flask method in two independent laboratories, which are also consistent with the literature data. It was also found that this new technique gives a number of advantages such as providing an accurate measurement of logD value, a much shorter experimental time and a smaller sample size required. With this approach, the formation of a problematic emulsion, commonly encountered in shake-flask experiments, is eliminated. It is envisaged that this method could be applicable to the high throughput logD screening of drug candidates.
authors.affiliation: Surface and Catalysis Research Centre, School of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: C H
authors.initials: CH
authors.lastname: Yu
authors.forename: K Y
authors.initials: KY
authors.lastname: Tam
authors.forename: S C
authors.initials: SC
authors.lastname: Tsang
mesh_terms: D005290:Ferric Compounds / Q000032:analysis; D008280:Magnetics; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods; D000442:Octanols / Q000032:analysis*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000032:analysis*
chemical_list: D005290:Ferric Compounds; D000442:Octanols; D014867:Water; C000499:ferric oxide