Estimation of partition coefficients

Both the Chen and Gross [48] and the Gallo et al. [49] methods have been applied to eliminating compartments. Both derivation methods are based on the specific mass balance equations for the given model structure. Monte Carlo investigations have demonstrated that both methods provide reasonably accurate and precise estimates of partition coefficients from concentration-time data sets containing error, data one is likely to encounter from in vivo studies. 

JM Gallo, FC Lam, DG Perrier. Area method for the estimation of partition coefficients used in physiological pharmacokinetic models. J Pharmacokin Biopharm 15 271-280, 1987. 

The following correlation equations were used in the estimation of partition coefficients used in this paper. 

Junghans, M. and Pretsch, E. (1997) Estimation of partition coefficients of organic compounds local database modeling with uniform-length structure descriptors. Fresenius Journal of Analytical Chemistry, 359, 88-92. 

The liquid phase and polymer phase activity coefficients were combined from different methods to see if better estimation accuracy could be obtained, since some estimation methods were developed for estimation of activity coefficients in polymers (e.g. GCFLORY, ELBRO-FV) and others have their origins in liquid phase activity coefficient estimation (e.g. UNIFAC). The UNIFAC liquid phase activity coefficient combined with GCFLORY (1990 and 1994 versions) and ELBRO-FV polymer activity coefficients were shown to be the combinations giving the best estimations out of all possible combinations of the different methods. Also included in Table 4-3 are estimations of partition coefficients made using the semi-empirical group contribution method referred to as the Retention Indices Method covered in the next section. 

Ethanol and aqueous ethanol mixtures play important roles as food simulants for the determination of migration of substances from packaging into foods. Depending on the polarity of the plastic one can use pure ethanol (for nonpolar plastics) or aqueous ethanol mixtures up to 50/50 % (for polar plastics) as alternative simulants to edible oils (see Chapters 9,10 and 11). The estimation of partition coefficients in poly-mer/simulant systems is consequently of practical importance. It is possible to do this for polyolefins in contact with alcohol and aqueous alcohol mixtures with the help of an equation analogous to Eq. (4-100) (Piringer, 1993) ... 

Baner, A. L. The estimation of partition coefficients, solubility coefficients and permeability coefficients for organic molecules in polymers using group contribution methods. New Developments in the Chemistry of Packaging Materials. ACS Symposium Dallas 1998. ACS Symposium Series, ACS Washington D.C. 1999. 

Estimation of log P by using quantitative structure property relationships (QSPR) modeling and molecular descriptors (described above) has resulted in a number of highly accurate methods. Methods involving MLR, PLS, and artificial neural network ensembles (ANNE) modeling have been reviewed.In summary, estimation of partition coefficient has now reached a stage where the error associated with estimation is approximately equal to experimental error and reliable estimates can be obtained in silico. 

Bodor, N. and Huang, M.-J. (1992b). An Extended Version of a Novel Method for the Estimation of Partition Coefficients. LPharmSci., 81,272-281. 

Huuskonen JJ, Livingstone DJ, Tetko IV. Neural network modeling for estimation of partition coefficient based on atom-type electrotopological state indices. I Chem Inf Comput Sci 2000 40 947-55. 

N. Bodor and M.-J. Huang, An extended version of a novel method for the estimation of partition coefficients, J. Pham. Sci. 81 212 (1992). 

Devillers, J. (2000) EVA/PLS versus autocorrelation/ neural network estimation of partition coefficients. Persp. Drug Disc. Des., 19, 117-131. 

Accurate values of Pow are clearly necessary for the ultimate calibration of all surrogate systems, but, in practice, direct measurements of Powby the traditional shake-flask method are seldom used. Particularly for compounds with low water solubility, experimental difficulties may arise from problems in phase separation without carryover, sorption to glass surfaces, or from formation of emulsions. All of these introduce serious uncertainties into the concentrations in the appropriate phases, and may consequently lead to substantial errors in the estimates of partition coefficients. The problem is particularly acute for compounds with extremely low solubility in water such as the chlorinated dibenzo[l,4]dioxins for which widely varying values have been reported (Marple et al. 1986 Shiu et al. 1988). For such compounds, use of a generator column has been advocated (De Voe et al. 1981 Woodburn et al. 1984). In essence, the following steps are carried out (1) a solution of the test substance in octanol is equilibrated with water and the concentration in the octanol phase is determined, (2) the octanol phase is... 

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