Log D

A certain balance of lypophilicity and hydrophilicity is required for a successful drug candidate – for solubility in aqueous biological fluids, on one hand, and for the ability to penetrate lipid bilayers of cell walls, on the other hand.  A widely used physico-chemical model for this is the partition of a compound between two immiscible solvents, typically pH-buffered water and n-octanol.  Partition coefficient (LogP) is a logarithm of the ratio of concentrations of the unionized (neutral) form of the compound in aqueous and organic media.  For ionizable compounds, the partition is a function of pH, and in this case the distribution coefficient (Log D), corresponding to the total partition of both ionized and unionized form, is used.  Log P is widely used in cheminformatics (LogP is a component of the Lipinski’s “rule of five”).  LogD is more convenient for practical measurements, as it takes into account solution pH, which is important for the analysis of the drug candidate’s properties in various biologic media having different pH values.

Service details
We use the miniaturized shake-flask method for LogD/LogP determination.  Incubations are carried out in Eppendorf  microtubes in duplicates. The most commonly used protocol is as follows: 10 μL aliquot of 10 mM DMSO compound stock is dissolved in the previously mutually saturated* mixture containing 990 μL of PBS buffer (pH 7.4) and 100 μL of octanol followed by mixing in a rotator for 1 hour at 30 rpm, and then the concentrations of the compounds in each solvent are measured by LC-MS (API3000, AB Sciex). Other pH buffers and customized assay setups, including a robotic high-throughput protocol, are available upon request.

Calculations of the partition ratios (peak area of the analyte in octanol phase to the peak area of the analyte in PBS buffer). Full study report is provided.

Sample Requirement/Submission
A minimal weighted amount of dry compound, 1 mg, or 100 µL of 10mM stock DMSO solution, is required for this assay.


* Reaching equilibrium between aqueous and octanol phases may take much longer time than partition of a tested compound between the same phases. For this reason, mutual saturation of aqueous and octanol phases is important for stable and reliable LogD/LogP measurements.