Partition coefficients potentiometric

Slater, B., McCormack, A., Avdeef A., Comer, J. E. pH-metric logP. 4. Comparison of partition coefficients determined by HPLC and potentiometric methods to literature values. J. Pharm. 

The pH-metric technique used to determine partition coefficients was first used in the 1950s in solvent extraction of metal complexes [280-282], but it is in pharmaceutical research that it is most widely used thanks to the recent development of a fully automated and computer-controlled apparatus [125,283]. The potentiometric approach has been validated in various solvent systems [284-287], and it has become a relevant and expanding experimental technique to obtain lipophilicity descriptors [257,287-289]. 

We considered micro-pA), values in Section 3.6. A parallel concept applies to partition coefficients (of multiprotic molecules) namely, if an ionizable substance of a particular stoichiometric composition can exist in different structural forms, then it is possible for each form to have a different micro-log P [224,243,273,275], When logP is determined by the potentiometric method (below), the constant determined is the macro-log P. Other log/1 methods may also determine only the macroscopic constant. 

Johansson, P.-A. Gustavii, K., Potentiometric titration of ionizable compounds in two phase systems. 2. Determination of partition coefficients of organic acids and bases, Acta Pharm. Suecica 13, 407 -20 (1976). 

Liu, X., Bouchard, G., Girault, H.H., Testa, B. and Carrupt, P.A. (2003) Partition coefficients of ionizable compounds in o-nitrophenyl octyl ether/ water measured by the potentiometric method. Analytical Chemistry, 75, 7036-7039. 

The pKa values of perhydropyridof 1,2-a]pyrazin-l -one, its 2-methyl derivative and their N-5 oxides were determined by potentiometric titration in a 4 1 mixture of 2-methoxyethanol and H20 (81BAP423).The partition coefficients of 3-substituted 2,3,4,4a,5,6-hexahydro-l//-pyrazino[l,2-a]-quinolines have been determined in water-l-octanol [80IJC(B)879],... 

Mirrlees MS, Moulton SJ, Murphy CT et al. (1976) Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography. J Med Chem 19 615-619 Pagliara A, Khamis E, Thrinh A et al. (1995) Structural properties governing retention mechanisms on RP-HPLC stationary phases used for lipophilicity measurements. J Liquid Chromatography 18 1721-1745 Slater B, McCormack A, Avdeef A et al. (1994) pH-Metric log P. 4. Comparison of Partition Coefficients Determined by Shake-Flask, HPLC and Potentiometric Methods. J Phar-maceut Sci 83 1280-1283... 

Using the potentiometric titration approach (the same approach is also used to determine logPow values and described in the paragraph about physicochemical properties), first the substance in aqueous solution is titrated against standard acid or base in order to obtain the pKa value. In presence of liposomes, the experiment is repeated and a shift in the observed pKa value (pKaapp ) might be noted as analyte has disappeared from the aqueous phase into the liposome phase. From the shift in observed pKaapp value the partition coefficient of protonated analyte and neutral analyte can be calculated (Pember van Balen et al. 2004). 

Clarke, F.FI. Cahoon, N.M. Partition coefficients by curve fitting the use of two different octanol volumes in a dual-phase potentiometric titration. J. Pharm. Sci. 1996, 85, 178-183. 

Computerized method provides convenient and accurate determination of the ionization constant in aqueous solution and of the apparent ionization constant in the presence of octanol. From these parameters, partition coefficients and apparent partition coefficients are easily calculated and agree with data reported using the shaker technique or HPLC. The curve-fitting method has been applied to the differential titration technique in which the solvent curve is subtracted from the solution curve before calculations are begun. This method has been applied to the potentiometric titration of aqueous solutions of the salts of bases with very low solubility in water. 

Potentiometric H2O Testa B and Murset-Rossetti L, The partition coefficient of protonated... 

Potentiometric H2O Seiler P, Bischuff O and Wagner R, Partition coefficients of 5-... 

Potentiometric H2O Seiler P, Simultaneous determination of partition coefficient and... 

Quigley JM, Jordan CGM and Timoney RF, The synthesis, hydrolysis kinetics and lipophilicity of O-acyl esters of propranolol, Int. J. Pharm., 101,145-163 (1994). NB Potentiometric titrations were also done in die presence of octanol the difference gave the partition coefficient. Also reported values for a series of propranolol esters. 

The pKa values of some antiinflammatory arylaliphatic acids, including alclofenac and ibuprofen, were measured potentiometrically in dimethyl sulfoxide/water. The values were confirmed by assessing the solubility of the acids as a function of the pH of the aqueous solutions. In this way, the intrinsic partition coefficient in octanol/ water was defined."... 

---