Octanol, partition coefficient measurements

FIGURE 3.18 Water-octanol partition coefficients measured and calculated by CLOGP. [Graph reconstructed from data by Yang et al., J. Pharm. Sci., 91, 517 (2001).]... 

Octanol" and "Membrane" pK in Partition Coefficients Measurement 67 Tab. 3.1 Octanol-water and liposome-water partition coefficients. ... 

Olive oil was the original model lipid for partition studies, and was used by Overton in his pioneering research [518,524], It fell out of favor since the 1960s, over concerns about standardizing olive oil from different sources. At that time, octanol replaced olive oil as the standard for partition coefficient measurements. However, from time to time, literature articles on the use of olive oil appear. For example, Poulin et al. [264] were able to demonstrate that partition coefficients based on olive oil-water better predict the in vivo adipose-tissue distribution of drugs, compared to those from octanol-water. The correlation between in vivo log Kp (adipose tissue-plasma) and log (olive oil-water) was 0.98 (r2), compared to 0.11 (r2) in the case of octanol. Adipose tissue is white fat, composed mostly of triglycerides. The improved predictive performance of olive oil may be due to its triglyceride content. 

Garst, J.E. (1984) Accurate, wide-range, automated, high-performance chromatographic method for the estimation of octanol/water partition coefficients. II Equilibrium in partition coefficient measurements, additivity of substituent constants, and correlation of biological data. J. Pharm. Sci. 73, 1623-1629. 

Marple, L., Berridge, B., and Throop, L. Measurement of the water-octanol partition coefficient of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Environ. Sci. Technol, 20(4) 397-399,1986. 

Different balance between intermolecular forces can be accessible via partition coefficients measured in solvents systems other than the traditional 1-octanol/water. Therefore there was a growing interest in the partition processes in several solvent/ water systems [64, 65] and in particular the critical quartet of solvents which was designed to merge the main information about a solute concerning its partition and transport. Only a few studies have been performed to characterize the lipophilicity profile of new chemical entities in different solvent/water systems and consequently the number of methods attempting to model such partitioning systems is limited. 

Marple L, Berridge B, Throop L. 1986a. Measurement of the water-octanol partition coefficient of... 

Determination of Octanol/Water Partition Coefficients. Since oc-tanol/water partition coefficient data for trifluoromethanesulfonanilide (I) and its substituted derivatives have not been reported in the literature and since it was not apparent that any of the substituent tt values previously determined by Fujita et al. (11) would be directly applicable to the TFMS herbicidal system, all TFMS partition coefficients and tt values were determined experimentally. The fluoroalkanesulfonanilides are very acidic because of the electron-withdrawing power of the parent fluoro-alkanesulfonyl group (5). The parent TFMS compound (I), for example, has a pKa in water of 4.45 at 25 °C. This inherent acidity extends to all TFMS series members and requires that the usual partition coefficient measurement procedure described by Fujita et al. (11) be modified to obtain accurate values of log P and tt. 

Lipophilicity is an important characteristic of organic compounds with interesting biological and pharmacological activity. Various determination methods are used to determine lipophilicity. Hansch et al. proposed the use of log P [139], the ratio of concentrations of the component in two phases, more exactly the octanol-water partition coefficient, measured with the shaken flask method. 

Thin-layer radiochromatography (radio-TLC) is widely applied for a variety of environmental studies involving radiolabeled pesticides, such as plant uptake from soil, bioaccumulation in fish, dissipation from soil, metabolism in soil, plants, and fish, and environmental fate. The determination of the lipophiUdty of pesticides is important because their bioaccumulation and tendency for degradation and biotransformation are related to lipid solubility. TLC has advantages for lipohilicity studies compared to traditional partition coefficient measurement in an octanol-water system. 

A drug is absorbed through diffusion across a series of separate barriers where the single layer of epithelial cells is the most significant barrier to absorption. Many in vitro methods have been developed for the study of this phenomenon. These methods include small animal gut studies, cell culture (i.e., Caco-2 cell culture model), octanol-water partition coefficients, measures of hydrogen bonding and desolvation energies, immobilized artificial membranes, and retention time on reversed-phase HPLC columns. 

Permeation-skin-gas chromatography (GC)/MS A silastic membrane was coated onto a fiber to be used as a permeation membrane. The MCF was immersed in the donor phase to partition the compounds into the membrane. At a given partition time, the MCF was transferred into a GC injector to evaporate the partitioned compounds for quantitative and qualitative analyses. This technique was developed and demonstrated to study the percutaneous permeation of a complex mixture consisting of 30 compounds. Each compound permeated into the membrane was identified and quantified with GC/MS. The standard deviation was less than 10% in 12 repeated permeation experiments. The partition coefficients and permeation rates in static and stirred donor solutions were obtained for each compound. The partition coefficients measured by this technique were well correlated (Pf — 0.93) with the reported octanol/water partition coefficients. This technique can be used to study the percutaneous permeation of chemical mixtures. No expensive radiolabeled chemicals were required. Each compound permeated into the membrane can be identified and quantified. The initial permeation rate and equilibrium time can be obtained for each compound, which could serve as characteristic parameters regarding the skin permeability of the compound. 

To test whether the barrier for steroids was the same as the barrier for the smaller solutes, Giorgi also measured the permeabilities and partition coefficients for some smaller molecules. Some of these data are reproduced in Fig. 10 as a log/log plot of permeabihty coefficients against n-octanol partition coefficients. Clearly the data for the small solutes and for the steroids fall on a fairly good straight line, suggesting that the same rate law holds for the permeation of the steroids as for that of the smaller solutes. All seem to encounter a rate-limiting permeability barrier which has... 

The determination of the lipophilicity of pesticides is important because their bioaccumulation and tendency for degradation and biotransformation are related to lipid solubility. TLC has advantages for lipophilicity studies compared to traditional partition coefficient measurement in an octanol-water system. 

For all enkephalin conjugates, we have determined the water/octanol partition coefficient (log P values) [61]. These values are a relative measure of lipophilicity of a compound. It must be noted that enkephalin as such is not able to cross the blood-brain barrier (BBB), very likely because of its fairly polar nature. It is only released in the CNS in proximity to the receptors from a larger peptide called preenkephalin. In comparison, the conjugates 27-29 are much more lipophilic, with log P values over 3.5 for 27 and 3.0 for the Mo complex 29. No difference in log P was found between the enkephalin diastereomers with Mo complexes derived from L-His or D-His. 

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