Distribution coefficients play a large role in the efficacy of a drug. Legal. 0000004979 00000 n So now youre left with a solution of compound B in ether. Extraction is a convenient method for separating an organic substance from a mixture, such as an aqueous reaction mixture or a steam distillate. This ratio is therefore a comparison of the solubilities of the solute in these two liquids. Here are my sample calculations. c+m/s1Y)kCW|xku+" pc 5_R=9.`oGzb T@0Zx"-/wg( 4XYHRe*>AN:hrX( %a([S|1fQ,**[^5,$9 Rnh3-=t3u1SLj. . Two liquids that can mix together are said to be miscible. 0000006769 00000 n [57][58], If the solubility, S, of an organic compound is known or predicted in both water and 1-octanol, then logP can be estimated as[46][59], There are a variety of approaches to predict solubilities, and so log S.[60][61], The partition coefficient between n-Octanol and water is known as the n-octanol-water partition coefficient , or Kow. oct/wat I highly recommend you use this site! Immiscible liquids are ones that cannot get mixed up together and separate into layers when shaken together. Solubility data can therefore be used to choose an appropriate solvent for an extraction. . In a multiple extraction procedure, a quantity of solvent is used to extract one layer (often the aqueous layer) multiple times in succession. An aqueous sample contains a complex mixture of organic compounds, all of which are at trace concentrations. If our goal is to extract a solute from the aqueous phase into the organic phase, there is one potential problem with using the distribution coefficient as a measure of how well you have accomplished this goal. when the compounds are added they usually decrease the dielectric constant of an aqueous phase, which leads to the formation of ion association complexes. 0000003679 00000 n (2), and the recovery rates for GPA (R 1) and IL (R 2) were defined by Eqs. (O/A = 1:1, T = 25 C, t = 30 min. | 9 distribution coefficient partition coefficient K=C1/C2=g compound per mL organic solvent/g compound per mL water K=1.5 any organic compound with an equilibrium distribution coefficient greater than 1.5 can be separated from water by extraction with a water insoluble organic solvent changing the solubility with acid base chemistry Uncharged metal Chelate complex formation. At the end of this guide I'll show you the sample calculations involving the distribution coefficient, Kd. Remember: salts are water soluble. Because in distillation the separation of compounds with large differences in their boiling point is separated. Taking the ratio of the compound's solubility in diethyl ether compared to water gives an approximate \(K\) of 4. The combined organic phases from several extractions (containing extractant) are treated with a fresh aqueous layer to remove the impurities. 0000001750 00000 n The calculation for the third extraction is as follows: \[4.07 = \dfrac{\left( \dfrac{x}{50 \: \text{mL ether}} \right)}{\left( \dfrac{0.09 \: \text{g} - x}{150 \: \text{mL water}} \right)}\]. As we will see shortly, this distribution of a solute between two immiscible phases forms the basis of chromatographic separations as well. The extraction efficiency of a metal ion in the presence of a ligand will depend on the pH of the aqueous phase. Salts B and C will wash away with the water while compound A remains in the ether. Finally this non-aqueous layer is removed and distilled to obtain the purified compound. The metal atom with positive charges aggregates themselves with negative charges to form neutral complexes. [7] The partitioning of a substance into a solid results in a solid solution. Water and organic solvents should not be miscible to each other. Note that with equal volumes of organic and aqueous phases, the partition coefficient represents the ratio of particles in each layer (Figure 4.11a). There are many situations where prediction of partition coefficients prior to experimental measurement is useful. of S in solvent B) By convention, the concentration of S in the aqueous phase is placed in the denominator. \[K = \dfrac{\text{Molarity in organic phase}}{\text{Molarity in aqueous phase}}\]. For example, EDTA is the most useful masking agent for anionic complex formation with several metal ions under specific conditions. Diazonium Salt | Preparation, Reactions & Uses. HS[o0~G8OyMd&V-euf$#1[kQbwizc9'@^B@qA-,`'Z>mb `-[s. OL.1"1D6c'XtM0!Zai=,TE [citation needed]. [15][bettersourceneeded] They are sorted by the partition coefficient, smallest to largest (acetamide being hydrophilic, and 2,2',4,4',5-pentachlorobiphenyl lipophilic), and are presented with the temperature at which they were measured (which impacts the values). So be sure to vent your sep funnel every few shakes! o Most other things will dissolve in the organic phase. Acid-Base Extraction: It is suitable for the extraction of amines. Before you turn on or turn off the vacuum open the hatch to allow air into the system. Both diethyl ether and benzene at first glance appear to be poor choices for extraction because caffeine is more soluble in water than in either solvent (if a gram of caffeine dissolves in \(46 \: \text{mL}\) water, but \(100 \: \text{mL}\) of benzene, caffeine is more soluble in water). It can be used to separate minute quantities of almost every metal from its ores. 660 28 { "01_Liquid-Liquid_Extraction" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "02_Chromatography_\u2013_Background" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "03_Broadening_of_Chromatographic_Peaks" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "04_Fundamental_Resolution_Equation" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "05_Liquid_Chromatographic_Separation_Methods" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "06_Gas_Chromatographic_Separation_Methods" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "07_Appendix_1:__Derivation_of_the_Fundamental_Resolution_Equation" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()" }, { "01_In-class_Problems" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "02_Text" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "03_Learning_Objectives" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "04_Instructor\'s_Manual" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "05_Out-of-class_Problems" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "06_Laboratory_Projects" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "07_Specialty_Topics" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()", "08_Vignettes" : "property get [Map MindTouch.Deki.Logic.ExtensionProcessorQueryProvider+<>c__DisplayClass228_0.b__1]()" }, [ "article:topic", "showtoc:no", "license:ccbyncsa", "licenseversion:40", "authorname:asdl", "author@Thomas Wenzel" ], https://chem.libretexts.org/@app/auth/3/login?returnto=https%3A%2F%2Fchem.libretexts.org%2FBookshelves%2FAnalytical_Chemistry%2FSupplemental_Modules_(Analytical_Chemistry)%2FAnalytical_Sciences_Digital_Library%2FCourseware%2FSeparation_Science%2F02_Text%2F01_Liquid-Liquid_Extraction, \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}}}\) \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash{#1}}} \)\(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\) \(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\)\(\newcommand{\AA}{\unicode[.8,0]{x212B}}\), status page at https://status.libretexts.org. The 's calculated using molarity and solubility values are not identical since different equilibria are involved. It plays a key role in Organic synthesis. The LibreTexts libraries arePowered by NICE CXone Expertand are supported by the Department of Education Open Textbook Pilot Project, the UC Davis Office of the Provost, the UC Davis Library, the California State University Affordable Learning Solutions Program, and Merlot. Figure 4.16 shows a diagram of an aqueous solution being extracted twice with diethyl ether. The partition coefficients reflect the solubility of a compound in the organic and aqueous layers, and so is dependent on the solvent system used. In most solvent extraction procedures the extraction of solute from an aqueous phase to an immiscible organic phase such as dichloromethane, hexane, and benzene. Knowing the value of \(K\), the value of \(x\) can be solved for using the equation below. indicates the pH-dependent mole fraction of the I-th form (of the solute) in the aqueous phase, and other variables are defined as previously. Hyoscyamine is an alkaloid from a plant in the nightshade family (Figure 4.13a), and is used medicinally to provide relief for a variety of gastrointestinal disorders. We also acknowledge previous National Science Foundation support under grant numbers 1246120, 1525057, and 1413739. In some cases the metabolites may be chemically reactive. [citation needed]. Solvent extraction is somehow different from distillation. xb```b``e`e``Kc`@ fd;#ThhD QB3$t^/P.%"TR2!X"|QDuE(li@utt4 2` :( I8@iu@h& endstream endobj 680 0 obj <>stream Acetanilide Structure, Uses & Hazards | What is Acetanilide? It can be calculated, %E=100 x millimoles of solute extracted/ total millimoles of the aqueous phase. 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Hydrophobic drugs with high octanol-water partition coefficients are mainly distributed to hydrophobic areas such as lipid bilayers of cells. After the ether boils away you are left with solid compound A. Salts, or anything with a charge, is going to dissolve in the aqueous phase. The partition coefficient generally refers to the concentration ratio of un-ionized species of compound, whereas the distribution coefficient refers to the concentration ratio of all species of the compound (ionized plus un-ionized). This result means that \(0.12 \: \text{g}\) is extracted into the diethyl ether in the second extraction and \(0.09 \: \text{g}\) remains in the aqueous layer \(\left( 0.21 \: \text{g} - 0.12 \: \text{g} \right)\). 8)", "Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system", "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", "Quantitative analysis of biochemical processes in living cells at a single-molecule level: a case of olaparibPARP1 (DNA repair protein) interactions", "The toxicity data landscape for environmental chemicals", "Lipophilicity--methods of determination and its role in medicinal chemistry", "Atomic Physicochemical Parameters for Three-Dimensional Structure-Directed Quantitative StructureActivity Relationships I. Partition Coefficients as a Measure of Hydrophobicity", "Computation of octanol-water partition coefficients by guiding an additive model with knowledge", "Simple method of calculating octanol/water partition coefficient", "A review of methods for the calculation of solution free energies and the modelling of systems in solution", "A comparison of log Kow (n-octanolwater partition coefficient) values for non-ionic, anionic, cationic and amphoteric surfactants determined using predictions and experimental methods", "Octanol-Water Partition Coefficient Measurement by a Simple, "Determination of liquid-liquid partition coefficients by separation methods", "Chapter 3: Solubility and Lipophilicity", List of boiling and freezing information of solvents, https://en.wikipedia.org/w/index.php?title=Partition_coefficient&oldid=1140367721, Short description is different from Wikidata, Articles with unsourced statements from June 2021, All articles needing additional references, Articles needing additional references from March 2016, Articles with unsourced statements from March 2016, Wikipedia articles needing factual verification from March 2016, Articles lacking reliable references from March 2016, Wikipedia articles needing page number citations from March 2016, Creative Commons Attribution-ShareAlike License 3.0, This page was last edited on 19 February 2023, at 19:59. After solving the algebra, \(x = \textbf{0.40 g}\). NaCl is widely used for this purpose. The distribution coefficient represents the equilibrium constant for this process. Your numbers will probably be different. distribution coefficient is very low, by repeated extractions with small volumes of solvent. This is a key method for the quantitative separation of elements in batch extractions. It is a critical parameter for purification using zone melting, and determines how effectively an impurity can be removed using directional solidification, described by the Scheil equation. In general, three extractions are the optimal compromise between expended effort and maximizing the recovery of material. BivL)`tU.g=&]kR|+/?Oo~3xzBu~mo#O G~mJ'A2 <0 The determination of the selected antihypertensive drugs in human plasma samples with the novel solvent front position extraction (SFPE) technique is presented. {\displaystyle \log P_{\text{oct/wat}}^{I}} The round bottom flask shouldnt be more than ~40% full of solvent or else you will get bumping (solvent slashing around- youll lose product this way). and an aqueous solution of a weak base such as sodium bicarbonate. 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. However, the reverse is also possible. For example, morphine has a partition coefficient of roughly 6 in ethyl acetate and water.\(^2\) If dark circles represent morphine molecules, \(1.00 \: \text{g}\) of morphine would distribute itself as shown in Figure 4.11. Using \(K\), the calculation is identical to the previous discussion, differing only in the smaller volume of the organic layer (\(50 \: \text{mL}\) instead of \(150 \: \text{mL}\)). (Imagine using 100 mL of organic solvent relative to a volume of water equal to that in an Olympic-sized swimming pool). Devise a way to solubilize the organic anion shown below in the organic solvent of a two-phase system in which the second phase is water. (b) When 50 cc of chloroform is used in each of two stages, the amount unextracted is: xu = 1 * (KV / KV + L)2 = (1/20 * 100 divided by 1/20 * 100 + 50)2. In multiple extractions, the organic layers are combined together,as the goal is to extract the compound into the organic solvent. Dont even worry about what that means yet. \[\mathrm{D_M = \dfrac{mol_{org}}{mol_{aq}}}\], \[\mathrm{D_C = \dfrac{mol_{org}\times V_{aq}}{mol_{aq}\times V_{org}} = D_M\left(\dfrac{V_{aq}}{V_{org}} \right )}\]. the two solvents, called the distribution coefficient, is characteristic of the compound and of the solvent pair. In other words, in two extractions using the same 100 cc ether we can separate (2/3 + 2/9), or 88.9%, of the original amount of the compound. This result means \(0.04 \: \text{g}\) remains in the aqueous layer \(\left( 0.09 \: \text{g} - 0.05 \: \text{g} \right)\) after the third extraction. I A generalized formula can be easily suggested for the amount remaining unextracted after a given number of operations. Some important factors are discussed as follows; It is considered the most important factor for the extraction of elements in designing a particular extraction procedure. Give it a try! Let V cc of a solution containing x0 grams of a substance be extracted with L cc of solvent. Most organic products arent, but its possible that a compound is so polar that its soluble in water. (3) and (4), respectively. LLE is an extraction of a substance from one liquid into another liquid phase. The particulate ratio is not as simple when the layer volumes are different, but the ratio of concentrations always equals the \(K\) (Figure 4.11b). How to tell if a compound is a salt you ask? The purpose of this lab is to do the experiment and subsequent calculation to prove this fact. It is a simple non-destructive and widely used technique in the laboratory. Because in distillation the separation of compounds with large differences in their boiling point is separated through the heating- condensation method. Furthermore, there exist also approaches using maximum common subgraph searches or molecule kernels. Liquid-liquid extraction involves the exchange of certain com- pounds between two solvents that are immiscible or only partially miscible. The distribution or partition coefficient, K d, measured at equilibrium, is a useful concept that expresses the relative affinity for a sorbate in solution to sorb to a particular solid. Polarized liquid interfaces have been used to examine the thermodynamics and kinetics of the transfer of charged species from one phase to another. Neutrals Whether the pH is acidic or basic, these will remain neutral under all circumstances. It is a simple and easily performable classical technique. The organic phase and aqueous phase form layers in your sep funnel. QSAR equations, which in turn are based on calculated partition coefficients, can be used to provide toxicity estimates. The extraction is repeated two to three times, or perhaps more times if the compound has a low partition coefficient in the organic solvent. [35] In the field of hydrogeology, the octanolwater partition coefficient Kow is used to predict and model the migration of dissolved hydrophobic organic compounds in soil and groundwater. However, benzene and acetone can also be used. Lets say you did some reaction and got the following compounds as your products, and lets say A is the product we want. [31][32] On the other hand, hydrophobic drugs tend to be more toxic because they, in general, are retained longer, have a wider distribution within the body (e.g., intracellular), are somewhat less selective in their binding to proteins, and finally are often extensively metabolized. When equilibrium has established, the ratio of concentration of solute in each layer is constant for each system, and this can be represented by a value \(K\) (called the partition coefficient or distribution coefficient). SNDc%Aqw_|/ZX&lCJb|Q[lnl)6=acT*/7]g8 For example, imagine that caffeine (Figure 4.12) is intended to be extracted from tea grounds into boiling water, then later extracted into an organic solvent. [25] Hence, the log P of a molecule is one criterion used in decision-making by medicinal chemists in pre-clinical drug discovery, for example, in the assessment of druglikeness of drug candidates. It is often convenient to express the log D in terms of PI, defined above (which includes P0 as state I = 0), thus covering both un-ionized and ionized species. Now titrate the aqueous layer with NaOH to determine how much benzoic acid remained in the water. This page titled Liquid-Liquid Extraction is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Thomas Wenzel. All other trademarks and copyrights are the property of their respective owners. Two main methods exist. "Extraction" refers to transference of compound (s) from a solid or liquid into a different solvent or phase. I [44][45] This strategy requires methods for the determination of concentrations in individual cells, i.e., with Fluorescence correlation spectroscopy or quantitative Image analysis. (ii) Now let's use 100 cc of ether in two successive extractions, using 50 cc each time. "A:! qO-Qjz Ht;o0{-)R\\AK C:$uB-I[@~Y{h;H*,~ &_dVtJH#wh@XHz(GM"+o*@gm>i IY'(_G~b ?%8IadOdJ4 )7i