Titration two-phase

Poloxamers are used primarily in aqueous solution and may be quantified in the aqueous phase by the use of compleximetric methods. However, a major limitation is that these techniques are essentially only capable of quantifying alkylene oxide groups and are by no means selective for poloxamers. The basis of these methods is the formation of a complex between a metal ion and the oxygen atoms that form the ether linkages. Reaction of this complex with an anion leads to the formation of a salt that, after precipitation or extraction, may be used for quantitation. A method reported to be rapid, simple, and consistently reproducible [18] involves a two-phase titration, which eliminates interferences from anionic surfactants. The poloxamer is complexed with potassium ions in an alkaline aqueous solution and extracted into dichloromethane as an ion pair with the titrant, tet-rakis (4-fluorophenyl) borate. The end point is defined by a color change resulting from the complexation of the indicator, Victoria Blue B, with excess titrant. The Wickbold [19] method, widely used to determine nonionic surfactants, has been applied to poloxamer type surfactants 120]. Essentially the method involves the formation in the presence of barium ions of a complex be-... 

The chemical properties of the alkylarylsulfonates are used in its analytical determination. As anions, LAS and other anionic surfactants react with large cations to salts, which are soluble in organic solvents (e.g., CHC13). By analysis it can be seen that cations such as Hyamine 1622 (25) and methylene blue, which rearrange with LAS to complex (26), are widely spread. These reactions are the basis for the so-called two-phase titration, an extensively used method... 

A number of proven methods is available for the analysis of commercial alkanesulfonates. The total sulfonate content and the monosulfonate content can be determined quite accurately by extractive methods and different forms of two-phase titration. 

The two-phase titration is based on the reaction of anionic surfactants with cations—normally large cationic surfactants—to form an ion pair. The preferred cationic is benzethonium chloride (Hyamine 1622, 1) because of the purity of the commercially available product. On neutralization of the ionic charges, the ion pair has nonpolar character and can be extracted continuously into the organic phase, e.g., chloroform, as it is formed. The reaction is monitored by addition of a water-soluble cationic dye, dimidium bromide (2), and a water-soluble anionic dye, disulfine blue (3). The cationic dye forms an extractable... 

Recently, several modifications of the two-phase titration and their precisions have been compared. The two-phase titration with the above-mentioned mixed indicator system, dimidium bromide/disulfine blue, is standardized in DGF (Deutsche Gesellschaft fur Fettforschung) and DIN methods, and is less time consuming and simpler than the standard gravimetric and extraction methods [18]. 

When performing the two-phase titration with benzethonium chloride in alkaline medium and in the presence of phenolphthalein as indicator, not only the monosulfonates but also the di- and polysulfonates are determined [19]. The content of di- and polysulfonates is the difference between two titration results giving the amounts of total sulfonates and monosulfonates. Identifying the endpoint requires some experience. 

A ring test proved that surfactant-selective electrodes are suitable for quantitative determination of anionic surfactants including alkanesulfonates [21]. The precision of this method, however, does not yet correspond to the state-of-the-art of the two-phase titration. Therefore, further development is needed to enhance the reproducibility and competitiveness of surfactant-sensitive titration. 

The method developed by Epton [212,213] became the universally accepted method for the analysis of active matter of anionic and cationic surfactants. Epton s method, also known as the two-phase titration, is based on the titration of the anionic surfactant with cetylpyridinium bromide, a cationic surfactant, in the presence of methylene blue as indicator. A solution of the anionic surfactant is mixed with the indicator dissolved in dilute sulfuric acid, followed by further addition of chloroform, and then it is titrated with the cationic surfactant. Methylene blue forms a complex with the anionic salt that is soluble in chloroform, giving the layer a blue color. As the titration proceeds there is a slow transference of color to the water layer until the equivalence point. At the equivalence point colors of the chloroform and water layers are visually the same. On successive additions of titrant the chloroform layer lightens in shade and finally becomes colorless. 

The two-phase titration method is still the most commonly used method, but due to the current concern regarding the health risks of chloroform, nowadays efforts are being devoted to develop an alternative standard method. This subject is on the agenda of the CESIO (Comite Europeen des Agents de Surface et leurs Intermediaries Organiques) Analysis Working Group. 

A manual titrimetric method using methyl orange as indicator and sodium tetraphenylboron as titrant has been described [273]. Dodecyl sulfate at concentrations of approximately 10"5 M have been analyzed by a visual two-phase titration in the presence of dichloroethane and tetrabromophenolphthalein ethyl ester [274]. 

ISO 2271 1989, Surface active agents Determination of anionic-active matter by manual or mechanical direct two-phase titration procedure. 

Two-phase titration is an old but very good method requiring no special apparatus [50]. 

Highly concentrated ether carboxylic acids with a low degree of ethoxylation even at room temperature can give an esterification reaction with the non-converted nonionic, especially with the fatty alcohol, to several percentage points. The result may be that a too low value is found for the ether carboxylate content. This mistake in analysis can be avoided by saponification of the formed ester [238]. Two hundred to 300 mg matter and ca 100 mg NaOH were weighed in a 50-ml Erlenmeyer glass, heated with 20 ml ethanol under reflux, and after cooling supplied with water to 100 ml. Afterward a two-phase titration was carried out. 

Active matter (anionic surfactant) in AOS consists of alkene- and hydroxy-alkanemonosulfonates, as well as small amounts of disulfonates. Active matter (AM) content is usually expressed as milliequivalents per 100 grams, or as weight percent. Three methods are available for the determination of AM in AOS calculation by difference, the two-phase titration such as methylene blue-active substances (MBAS) and by potentiometric titration with cationic. The calculation method has a number of inherent error factors. The two-phase titration methods may not be completely quantitative and can yield values differing by several percent from those obtained from the total sulfur content. These methods employ trichloromethane, the effects from which the analyst must be protected. The best method for routine use is probably the potentiometric titration method but this requires the availability of more expensive equipment. 

The technique is especially useful for analysis of low molecular weight AOS (C8, C10), which has greater water solubility, and can be more accurate than the two-phase titration procedures. High molecular weight AOS with poor water solubility can still be analyzed if the ion exchange is performed at elevated temperature. 

Gravimetric and volumetric methods are practicable for the quantitative determination of the a-sulfo fatty acid esters. Using gravimetric methods the surfactant is precipitated with p-toluidine or barium chloride [105]. The volumetric determination method is two-phase titration. In this technique different titrants and indicators are used. For the analysis of a-sulfo fatty acid esters the quaternary ammonium surfactant hyamine 1622 (p,f-octylphenoxyethyldimethyl-ammonium chloride) is used as the titrant [106]. The indicator depends on the pH value of the titration solution. Titration with a phenol red indicator is carried out at a pH of 9, methylene blue is used in acid medium [106], and a mixed indicator of a cationic (dimidium bromide) and an anionic (disulfine blue VN150) dye can be used in an acid and basic medium [105]. 

Analytical methods for qualitative and quantitative determination of all kinds of surfactants have long been established. There can be found either wet chemical methods—like titration—or methods of instrumental analytics. A classical method for anionic surfactants is the so-called two-phase-titration [63]. Using this method nearly every molecule bearing an anionic group is detected. The correct determination of sulfosuccinates is limited to the interferences of the other ingredients and byproducts present. With few exceptions all sulfosuccinates react with special indicators, e.g., hyamin 1622 (Rohm and Haas), to form an anionic-cationic complex and hence are to be analyzed by active content titration. 

Active content ( pure sulfosuccinate, as analyzed by a two-phase titration assuming a defined molecular weight) 32-35%... 

Although Eq. (25) has no physical meaning and although its simplification is not valid thermodynamically, since the condition of electroneutrality in both phases is not fulfilled if the proton cannot partition, it agrees very well with experimental data, which justifies its use. In fact, computerized fitting procedures correct for this error in commercial two-phase titrators, so that the experimental value of p K can directly be introduced in Eq. (25). 

The measurement of absorbance of light by a dyestuff-anionic surfactant complex, which has been extracted into an organic solvent is a key feature of many methods, and Sodergren has successfully used segmented flow colorimetry for an automated version of this procedure (2 ). An alternative is the two phase titration technique, pioneered by Herring (3) which uses dimidium... 

BASIS OF MANUAL PHOTOMETRIC TITRATION. The determination of anionic surfactants by a photometric titration employs a cationic indicator to form a coloured complex with the surfactant which is insoluble in water but readily soluble in chlorinated solvents (1 ). The end point of the titration occurs when there is a loss of colour from the organic phase. A considerable improvement in this technique is achieved by the use of a mixture of anionic and cationic dyes (4 ), for example disulphine blue and dimidium bromide (Herring s indicator (3)). The sequence of colour changes which occurs during the two phase titration of an anionic surfactant (AS) with a cationic titrant (CT) using a mixed indicator consisting of an anionic indicator (AD) and cationic indicator (CD) is summarised in Scheme 1 ... 

The sulfonate content was determined either by the well-known technique of two-phase titration with hyamine or by liquid chromatography (HPCL). Nonionic surfactants were analyzed by HPLC (16) in the reverse or normal phase mode depending on whether the aim was to determine their content in effluents or to compare their ethylene oxide distribution. 

Massaccesi reported the development of a two-phase titration method for the analysis of miconazole and other imidazole derivatives in pure form and in pharmaceutical formulation [14], To the sample (10 mg) are added 10 mL of water, 10 mL of 1 M-sulfuric acid, 25 mL of dichloromethane and 1 mL of 0.05% indophenol blue (C.I. No. 49700) in dichloromethane solution and the solution is titrated with 10 mM sodium dodecyl sulfate until the color of the organic phase changes from blue to pale yellow. Results obtained for the drug in pure form, tablets, suppositories, cream and lotion agreed with the expected values and the coefficient of variation (n = 6) were 0.3-0.35%. Imidazole and the other constituents of the pharmaceutical preparations did not interfere. 

A special type of ISE is used in the two-phase titration [ 17, 50, 51, 52], in which the titrant (for example picric acid) is added to the aqueous phase containing the test ion (for example the trioctylethylammonium ion), which is in contact with a nitrobenzene phase containing picrate ions and functioning as an ISE. 

Wang, L.K. Direct two-phase titration method for analyzing anionic nonsoap surfactants in fresh and saline waters. J. Environ. Health 1975, 38, 159-163. 

The use of distribution coefficients for the QSAR treatment of ionizable compounds has been extended to consideration of ion-pair partitioning into biolipid phases. Two experimental methods for determining ion-pair partition coefficients are described. One is a single-phase titration in water-saturated octanol, in which case (for acids) log Pj = log P + pKa - pKa. The other is a two-phase titration (octanol/water) from which the ratio (P + 1)/(Pj + 1) can be calculated. An example outcome is that the uncoupling activity of phenols can be represented by an equation in log instead of log D and pKa. 

The two-phase titration was first described in 1963 (19) as a means to simultaneously determine a partition coefficient and pKa. Several variations have appeared since (20-24), but none has seemed to gain favor. I like the simplified approach of Clarke (25,26) who uses the method to determine partition coefficients after separately determining (or knowing) the pKa. 

Sometimes the log P from a two-phase titration using Equations 18 or 19 is low, compared with shake-flask values. We attribute this to ion-pair partitioning. The quadrant diagram. Figure 8, is helpful for developing the pertinent equations. The amount of each species in each phase is shown in the appropriate sector. 

Table IV. Partition Coefficients of Ion Pairs Determined by Two-Phase Titrations ...

These new methods for determining the partition coefficients of ionized species are still e3q>erimenta1, but they are presented in a spirit that they may stimulate thinking and further refinement. Single-phase titrations with HCl in octanol have only recently been run. A possible concentration dependency of pKa in the single-phase titrations has been suggested by a referee and will be looked for. Further refinement of the two-phase titrations may incorporate ion-pair association constants. 

Veinbergs et al. have reported a comparative study of the methods used for the determination of procaine in Celnovocaine by titrimetry and photometry [79]. Tsubouchi et al. have reported the application of singlephase endpoint change systems in two-phase titrations to the analysis of procaine and some other amines [80]. 

Wang has determined citric acid and procaine in Xiaozhi injectable (an anti-hemorrhoid agent) by two-phase titration [81]. With constant shaking, a mixture of 1 1 1 2 Xiaozhi solution - water - chloroform -ethanol was titrated against 0.1 M sodium hydroxide to the phenolphthalein end point, thus obtaining the citric acid content. Dilute nitric acid was then added to the solution until the pink color disappeared, and the solution titrated against 0.1 M silver nitrate (with 5 drops of... 

Medvedovskii et al. have developed a method of alkalimetric two-phase titration for the determination of procaine hydrochloride and other organic base salts [83]. 

The method of Koval chuk et al. was applied in the determination of procaine [84], These authors have also developed another alkalimetric two-phase titration method for determination of the salts of organic bases, including procaine hydrochloride [85]. A solution of the base salt was mixed with 2 mL chloroform and 2 drops of 0.15% methylene blue solution, and the mixture titrated with 0.02 to 0.1 M sodium hydroxide with shaking. At the endpoint, the chloroform layer becomes pink-violet. 

Carboxybetaines Low pH two-phase titration, gravimetric analysis, or potentiometric titration... 

There are a number of books [168-173] and reviews [68,174,175] that provide good starting points. Refs. [168,176-178] discuss methods for the determination of anionic surfactants, which are probably the most commonly encountered in industry. Most of these latter methods are applicable only to the determination of sulfate-and sulfonate-functional surfactants. Probably the most common analysis method for anionic surfactants is Epton s two-phase titration method [179,180] or one of its variations [171,172,181-183]. Additional references are provided elsewhere [163], Aqueous surfactant micellar systems have also been utilized successfully in virtually every area of analytical chemistry (for example, [184—186]). 

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