Potentiometric method, solubility determination

A potentiometric method for determination of ionization constants for weak acids and bases in mixed solvents and for determination of solubility product constants in mixed solvents is described. The method utilizes glass electrodes, is rapid and convenient, and gives results in agreement with corresponding values from the literature. After describing the experimental details of the method, we present results of its application to three types of ionization equilibria. These results include a study of the thermodynamics of ionization of acetic acid, benzoic acid, phenol, water, and silver chloride in aqueous mixtures of acetone, tetrahydrofuran, and ethanol. The solvent compositions in these studies were varied from 0 to ca. 70 mass % nonaqueous component, and measurements were made at several temperatures between 10° and 40°C. 

Singer JM, O Hare MJ, Rehm CR and Zarembo JE, Chlorthalidone, APDS, 14, 1-34 (1985) Fleurren ALJ, van Ginneken CAM and van Rossum JM, Differential potentiometric method for determining dissociation constants of very sli tly water soluble drugs applied to die sulfonamide diuretic chlorthalidone, /. Pharm. Sci., 68(8), 1056-1058 (1979). NB The sulfonamide function present in chlordialidone, is considered to be responsible for the acid dissociation. The ionization constant of chlorthalidone was determined based on spectrophotometric measurements of the concentration [chlor] at various pH values ... 

Potentiometry is used in the determination of various physicochemical quantities and for quantitative analysis based on measurements of the EMF of galvanic cells. By means of the potentiometric method it is possible to determine activity coefficients, pH values, dissociation constants and solubility products, the standard affinities of chemical reactions, in simple cases transport numbers, etc. In analytical chemistry, potentiometry is used for titrations or for direct determination of ion activities. 

We report here studies conducted with 58 crystalline drug-like compounds. The solubilities are of high quality, having been determined in only three laboratories using the same automated potentiometric method. However, the set is too small to... 

Drug dissociation constants are experimentally determined by manual or automated potentiometric titration or by spectrophotometric methods.40 Current methods allow determination of pXa values with drug concentrations as low as 10 to 100 pM. For highly insoluble compounds (concentration <1 to 10 pM), the Yesuda-Shedlovsky method41 is commonly used where organic cosolvents (i.e., methanol) are employed to improve solubility. The method takes three or more titrations at different cosolvent concentrations, and the result is then extrapolated to pure aqueous system. The dissociation constant can also be determined with less accuracy from the pH-solubility profile using the following modification of Henderson-Hasselbach equation ... 

A few recent reports have indicated that multiple cyclodextrin formation in aqueous solution is more common than once believed (1-8). Gelb et al. determined 1 2 (substratercyclodextrin CO ) bTnJing constant ratios but failed to obtain individual constant values (2). Connor et al. used potentiometric, spectrophotometric, solubility and competitive indicator methods to evaluate the binding constants of one substrate molecule bound to two CO molecules (5-7). Some of these methods gave substantial relative errors for the binding constants while other techniques were applicable to a limited number of compounds. 

Dissociation constants of ionizable components can be determined using various methods such as potentiometric titrations [85] CE, NMR, [86] and UV spectrophotometric methods [87]. Potentiometric methods have been used in aqueous and hydro-organic systems however, these methods usually require a large quantity of pure compound and solubility could be a problem. Potentiometric methods are not selective because if the ionizable impurities in an impure sample of the analyte have a pK similar to that of the analyte, this could interfere with determining the titration endpoint. If the titration endpoint is confounded, then these may lead to erroneous values for the target analyte pKa. 

With the potentiometric approach, determination of intrinsic solubility is based upon the measurement of the pH shift caused by compound precipitation during acid-base titration of ionizable compounds. Two commercial potentiometric methods currently available are pSol [30, 39] and Cheqsol [40-42], In the pSol method developed by Avdeef, a minimum of three titrations in the direction of dissolution are performed. Normal pH versus volume titration plots are reexpressed as Bjerrum plots, that is, average number of bound protons versus pH. The Bjermm plots enable the shift in compound pKa to be more readily observed and are used to determine intrinsic solubility (S0) via Equation 2.5 ... 

The acid-base equilibrium constants of the beta-blockers atenolol, oxprenolol, timolol, and labetalol were determined by automated potentiometric titrations. The pKg values were obtained in water-rich or water methanol medium (20% MeOH) to obviate the solubility problems associated with the compounds. The initial estimates of pKa values were obtained from Gran s method and then, were refined by the NYTIT and ZETA versions of the LETAGROP computer program. The resultant values were 9.4 (/ = 0.1 M KCI, 20% methanol) for atenolol, 9.6 (/ = 0.1 M KCI) for oxprenolol, 9.4 (/ = 0.1 M KCI, 20% methanol) for timolol and 7.4 and 9.4 (/ = 0.1 M KCI) for labetalol. The potentiometric method was found to be accurate and easily applicable. The operational criteria for applying the methodology are indicated. 

With the preliminary estimate of c just given, A is found to be 137.93, yielding with equation. (1) the slightly higher value, 1.306 X 10Bf for the solubility of silver chloride at 25°. This agrees, within experimental error, with the determination, described in Chapter 17, of the same quantity by Brown and Maclnnes using a potentiometric method. 

Papers devoted to the studies of metal-oxide solubilities in molten potassium halides are few. In particular, Guyseva and Khokhlov reported the determination of the solubility product of MgO in molten KC1 in the 1067-1195 K temperature range [374], The study was performed by the potentiometric method using the Pt(02) gas-oxygen electrode. The experimental method consisted of the addition of a known quantity of MgCl2 to the pure melt, and measurements of e.m.f. for the following cell ... 

As mentioned in Section 3.7.1.2, there is a considerable scatter of solubility product values obtained in the molten KCl-NaCl eutectic using different methods of solubility determination. This disagreement in the solubility parameters may be explained by differences in the sizes of oxide particles whose solubility is to be determined. The difference in size causes the scatter of the solubility data according to the Ostwald-Freundlich equation and the employment of the isothermal saturation method, which implies the use of commercial powders (often pressed and sintered), leads to values which are considerably lower than those obtained by the potentiometric titration technique where the metal-oxides are formed in situ. Owing to this fact, the regularities connected with the effect of physico-chemical parameters of the oxides or the oxide cations should be derived only from solubility data obtained under the same or similar experimental conditions. However, this does not concern the dissociation constants of the oxides, since homogeneous acid-base equilibria are not sensitive to the properties of the solid phase of... 

V.L. Cherginets and E.G. Khailova, Determination of Solubility Products of Oxides in Molten by Potentiometric Method with the Use of Metallic and Oxygen Electrodes, Zh. Neorg. Khim. 36 (1991) 1277-1280. 

V.M. Ivenko, Determination of Solubility of Barium Oxide in BaC12-KCl-NaCl Eutectic by Potentiometric Method (Abstract of 10th All-Union Conference on Physics, Chemistry and Electrochemistry of Ionic Melts and Solid Electrolytes, Ekaterinbourg, Vol. 1. 1992) p. 74. 

Most ligand pAa values can be determined via a potentiometric titration, where the pH is monitored after sequential additions of either acid or base. The requirement of millimolar ligand concentration is a major drawback of this method, especially for ligands with poor water solubility. Another common method for determination of protonation constants when a potentiometric titration is not possible is a spectrophotometric titration, where both pH and spectral changes are monitored upon the addition of acid or base. 

In aqueous solution pristinamycin 1 shows two acid-base equilibria (determined by potentiometric methods [41]) associated with (i) protonation of the dimethylamino function of the iV-methyl 4-dimethylaminophenylalanine residue - pKji =4.1 and (ii) deprotonation of the hydroxy group of the hydroxy-picolinic acid residue - pK,2 = 7.3. The molecule is neutral between pH = 4 and pH = 7 and is water soluble at pH less than 3 as the corresponding acid-salt. 

NiO solubility in molten KF-LiF at 550 C determined by potentiometric method is 1.3x10 This value considerably exceeds values obtained for the above chloride melts. The increase of NiO solubility occurred due to formation of fluoride complexes which are more stable than chloride ones. 

As well as these titrimetric methods, the AOAC details a potentiometric method that is also recommended in Codex Alimentarius standards. The vegetables or legumes are dispersed in water and acidified, with the soluble chlorides titrated potentiometrically with silver nitrate. Many instruments are also now available with ion-selective electrodes that can be applied to the determination of salt in foods. They offer reasonable accuracy with ease of use and are particularly suitable for quality assurance purposes. 

The gravimetric determination of potassium as its barely soluble tetraphenylborate is recommended and described here. This method has also been applied to seawater for an ocean-wide survey of the element (see Table 11-1). The procedure is preferred because of its high accuracy and precision and the minimum amount of equipment required to perform the analysis. Basically, the method outlined here is that developed by Wittig (1950) and Raff and Brotz (1951). A brief description of a potentiometric method is presented in Section 11.2.3.6. 

The solubility method for determining pKg is rather laborious but proves useful in those rare cases where (a) the substance is too insoluble in water for the potentiometric or conductimetric methods, and (/ ) the molecular and ionic ultraviolet spectra are either too similar or totally lacking. If the spectra are identical, this forms no barrier to their use for analysing the saturated solutions, which otherwise are examined by... 

The fluoride ion selective electrode is the most popular means of fluoride ion determination after sample destruction by any method but it does have limitations. It can be used either directly to measure the fluoride potential6 or as an end-point detector in a potentiometric titration with a lanthanum(l II) reagent as titrant.4,7 Problems can be experienced with potential drift in direct potentiometry, especially at low fluoride ion concentrations. Titration methods often yield sluggish end points unless water miscible solvents are used to decrease solubilities and increase potentia 1 breaks and sulfate and phosphate can interfere. End-point determination can be facilitated by using a computerized Gran plotting procedure.4... 

Tartaric Acid. Quantitative measures of total tartrate are useful in determining the amount of acid reduction required for high acid musts and in predicting the tartrate stability of finished wines. Three procedures may be used. Precipitation as calcium racemate is accurate (85), but the cost and unavailability of L-tartaric acid are prohibitive. Precipitation of tartaric acid as potassium bitartrate is the oldest procedure but is somewhat empirical because of the appreciable solubility of potassium bi-tartrate. Nevertheless, it is still an official AO AC method (3). The colorimetric metavanadate procedure is widely used (4, 6, 86, 87). Tanner and Sandoz (88) reported good correlation between their bitartrate procedure and Rebeleins rapid colorimetric method (87). Potentiometric titration in Me2CO after ion exchange was specific for tartaric acid (89). 

The measurement of pH in cheese making is extremely important to control fermentation/acid production and hence the final quality. While there are no standard methods available for measuring cheese pH, there have been few methods reported in the literature. One method involves preparing a slurry of 10 g of grated cheese in water and measuring the pH potentiometrically (Fox et al., 2004a). However, this method may alter the balance between colloidal and soluble calcium phosphate and hence it is preferable to measure the pH of the cheese directly. The quinhydrone electrode method (Marshall, 1992) measures the pH directly. The potential (mV) created by a paste of cheese and quinhydrone in saturated KC1 is measured and used to determine the pH at a particular temperature. 

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