title: Carrier Mediated Distribution System (CAMDIS): a new approach for the measurement of octanol/water distribution coefficients.
abstract: 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 D(oct). 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 log D(oct) values. Excellent agreement with literature data (r(2) = 0.996, standard error of estimate, SEE = 0.111), high reproducibility (standard deviation, SD < 0.1 log D(oct) units), minimal sample consumption (10 μL of 100 μM DMSO stock solution) and a broad analytical range (log D(oct) range = -0.5 to 4.2) make CAMDIS a valuable tool for the high-throughput assessment of log D(oc)t.
authors.affiliation: F. Hoffmann-La Roche Ltd., pRED, Pharma Research and Early Development, Pharmaceutical Research, Innovation Center Basel, CH-4070 Basel, Switzerland.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Wagner
authors.affiliation: F. Hoffmann-La Roche Ltd., pRED, Pharma Research and Early Development, Pharmaceutical Research, Innovation Center Basel, CH-4070 Basel, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Fischer
authors.affiliation: F. Hoffmann-La Roche Ltd., pRED, Pharma Research and Early Development, Pharmaceutical Research, Innovation Center Basel, CH-4070 Basel, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kansy
authors.affiliation: Biozentrum, University of Basel, Div. of Biophysical Chemistry, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Seelig
authors.affiliation: F. Hoffmann-La Roche Ltd., pRED, Pharma Research and Early Development, Pharmaceutical Research, Innovation Center Basel, CH-4070 Basel, Switzerland; Biozentrum, University of Basel, Div. of Biophysical Chemistry, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: frauke_assmus@hotmail.com.
authors.forename: Frauke
authors.initials: F
authors.lastname: Assmus
mesh_terms: D020003:1-Octanol / Q000737:chemistry*; D002623:Chemistry Techniques, Analytical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D015203:Reproducibility of Results; D014867:Water / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water; D020003:1-Octanol
keywords: CAMDIS; Concentration dependence; Filter support; Octanol/water distribution coefficient; Octanol/water partition coefficient; pH dependence