Editing Partition coefficient (section)

== Measurement ==
A number of methods of measuring distribution coefficients have been developed, including the shake-flask, separating funnel method, reverse-phase HPLC, and pH-metric techniques.<ref name = "Comer_2001"/>{{rp|280}}

=== Separating-funnel method ===
In this method the solid particles present into the two immiscible liquids can be easily separated by suspending those solid particles directly into these immiscible or somewhat miscible liquids.

=== Shake flask-type ===
The classical and most reliable method of log ''P'' determination is the ''shake-flask method'', which consists of dissolving some of the solute in question in a volume of octanol and water, then measuring the concentration of the solute in each solvent.<ref name = "Dearden_1988">{{cite journal | vauthors = Dearden JC, Bresnan GM | title = The Measurement of Partition Coefficients | journal = Quantitative Structure-Activity Relationships | date = 1988 | volume = 7 | issue = 3 | pages = 133–144 | doi = 10.1002/qsar.19880070304 }}</ref><ref name = "Andrés_2015">{{cite journal | vauthors = Andrés A, Rosés M, Ràfols C, Bosch E, Espinosa S, Segarra V, Huerta JM | title = Setup and validation of shake-flask procedures for the determination of partition coefficients (log ''D'') from low drug amounts | journal = European Journal of Pharmaceutical Sciences | volume = 76 | pages = 181–91 | date = August 2015 | pmid = 25968358 | doi = 10.1016/j.ejps.2015.05.008 | hdl = 2445/143737 | hdl-access = free }}</ref> The most common method of measuring the distribution of the solute is by [[UV/VIS spectroscopy]].<ref name = "Dearden_1988"/>

=== HPLC-based ===
A faster method of log ''P'' determination makes use of [[high-performance liquid chromatography]]. The log ''P'' of a solute can be determined by [[correlation|correlating]] its [[retention time]] with similar compounds with known log ''P'' values.<ref name="pmid15214672">{{cite journal | vauthors = Valkó K | title = Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution | journal = Journal of Chromatography A | volume = 1037 | issue = 1–2 | pages = 299–310 | date = May 2004 | pmid = 15214672 | doi = 10.1016/j.chroma.2003.10.084 }}</ref>

An advantage of this method is that it is fast (5–20 minutes per sample). However, since the value of log ''P'' is determined by [[linear regression]], several compounds with similar structures must have known log ''P'' values, and extrapolation from one chemical class to another—applying a regression equation derived from one chemical class to a second one—may not be reliable, since each chemical classes will have its characteristic [[parameter|regression parameters]].{{citation needed|date=March 2016}}

=== pH-metric ===
The pH-metric set of techniques determine lipophilicity pH profiles directly from a single acid-base titration in a two-phase water–organic-solvent system.<ref name = "Comer_2001"/>{{rp|280–4}} Hence, a single experiment can be used to measure the logarithms of the partition coefficient (log ''P'') giving the distribution of molecules that are primarily neutral in charge, as well as the distribution coefficient (log ''D'') of all forms of the molecule over a pH range, e.g., between 2 and 12. The method does, however, require the separate determination of the pK<sub>a</sub> value(s) of the substance.

=== Electrochemical ===

Polarized liquid interfaces have been used to examine the thermodynamics and kinetics of the transfer of charged species from one phase to another. Two main methods exist. The first is [[ITIES]], "interfaces between two immiscible electrolyte solutions".<ref name="pmid12948031">{{cite journal | vauthors = Ulmeanu SM, Jensen H, Bouchard G, Carrupt PA, Girault HH | title = Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system | journal = Pharmaceutical Research | volume = 20 | issue = 8 | pages = 1317–22 | date = August 2003 | pmid = 12948031 | doi = 10.1023/A:1025025804196 | s2cid = 9917932 | url = http://infoscience.epfl.ch/record/269694/files/11095_2004_Article_468694.pdf }}</ref> The second is droplet experiments.<ref>{{Cite journal| vauthors = Scholz F, Komorsky-Lovrić Š, Lovrić M |date=February 2000|title=A new access to Gibbs energies of transfer of ions across liquid{{!}}liquid interfaces and a new method to study electrochemical processes at well-defined three-phase junctions|url=https://linkinghub.elsevier.com/retrieve/pii/S1388248199001563|journal=Electrochemistry Communications|language=en|volume=2|issue=2|pages=112–118|doi=10.1016/S1388-2481(99)00156-3}}</ref> Here a reaction at a triple interface between a conductive solid, droplets of a redox active liquid phase and an [[electrolyte]] solution have been used to determine the energy required to transfer a charged species across the interface.<ref name="Bond_1994">{{cite journal | vauthors = Bond AM, Marken F | title = Mechanistic aspects of the electron and ion transport processes across the electrode | journal = [[Journal of Electroanalytical Chemistry]] | volume = 372 | issue = 1–2 | pages = 125–135 | year = 1994 | doi = 10.1016/0022-0728(93)03257-P }}</ref>

=== Single-cell approach ===

There are attempts to provide partition coefficients for drugs at a single-cell level.<ref>{{cite journal |title=Quantitative analysis of biochemical processes in living cells at a single-molecule level: a case of olaparib–PARP1 (DNA repair protein) interactions |journal=Analyst |date=2021 |doi=10.1039/D1AN01769A|last1=Karpińska |first1=Aneta |last2=Pilz |first2=Marta |last3=Buczkowska |first3=Joanna |last4=Żuk |first4=Paweł J. |last5=Kucharska |first5=Karolina |last6=Magiera |first6=Gaweł |last7=Kwapiszewska |first7=Karina |last8=Hołyst |first8=Robert |volume=146 |issue=23 |pages=7131–7143 |pmid=34726203 |s2cid=240110114 |url=https://eprints.lancs.ac.uk/id/eprint/161906/1/AN_ART_09_2021_001769.R1_Proof_hi.pdf }}</ref><ref name="karpinska">{{cite journal |title=Cellular Uptake of Bevacizumab in Cervical and Breast Cancer Cells Revealed by Single-Molecule Spectroscopy |journal=J. Phys. Chem. Lett. |date=2023 |doi=10.1021/acs.jpclett.2c03590|last1=Karpinska |first1=Aneta |last2=Magiera |first2=Gaweł |last3=Kwapiszewska |first3=Karina |last4=Hołyst |first4=Robert |volume=14 |issue=5 |pages=1272–1278 |pmid=36719904 |s2cid=256415374 |pmc=9923738 }}</ref> This strategy requires methods for the determination of concentrations in individual cells, i.e., with [[Fluorescence correlation spectroscopy]] or quantitative [[Image analysis]]. Partition coefficient at a single-cell level provides information on cellular uptake mechanism.<ref name="karpinska" />