Potentiometric titrations, automation

It must be realized that the constant current (-1) chosen virtually determines a constant titration velocity during the entire operation hence a high current shortens the titration time, which is acceptable at the start, but may endanger the establishment of equilibrium of the electrode potentials near the titration end-point in an automated potentiometric titration the latter is usually avoided by making the titration velocity inversely proportional to the first derivative, dE/dt. Now, as automation of coulometric titrations is an obvious step, preferably with computerization (see Part C), such a procedure can be achieved either by such an inversely proportional adjustment of the current value or by a corresponding proportional adjustment of an interruption frequency of the constant current once chosen. In this mode the method can be characterized as a potentiometric controlled-current coulometric titration. 

In routine analysis, often a one-dimensional so-called end-point titration can be automatically carried out up to a pre-set pH or potential value and with a previously chosen overall titration velocity in order to avoid overshoot, the inflection point should be sufficiently sharp and the titrant delivery must automatically diminish on the approach to that point in order to maintain equilibrium, and stop in time at the pre-set value. For instance, the Metrohm 526 end-point titrator changes both the dosing pulse length and its velocity by means of a pulse regulator in accordance with the course of the titration curve in fact, the instrument follows the titration two-dimensionally, but finally reports only a one-dimensional result. The Radiometer ETS 822 end-point titration system offers similar possibilities. However, automated titrations mostly represent examples of a two-dimensional so-called eqilibrium titration, where the titration velocity is inversely proportional to the steepness of the potentiometric titration curve hence the first derivative of the curve can usually also be recorded as a more accurate means of determining the inflection... 

Several approaches for higher-throughput lipophilicity measurements have been developed in the pharmaceutical industry [38], including automated shake-plate methods [46], and some of these are now available commercially [47]. A convenient method to measure octanol/water partitioning is based on potentiometric titration this is called the pH-method [48],... 

Potentiometric titrations are readily automated by using a motor-driven syringe or an automatic burette coupled to a chart recorder or digital printout system. This is described in more detail in Chapter 12. A micro-processor-controlled titrator is discussed in Chapter 13. 

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 ... 

For higher accuracy in the low polymer concentration range, two different methods were used. In the case of PAA, potentiometric titrations of solutions of PAA were performed with 0.01 N NaOH using a Brinkman model, Westbury, NY, automated titrator. Blank tests indicated no interfering species. Known amounts of PAA were used to prepare a calibration curve immediately after titration of the samples containing unknown amounts of polymer. The starting point of the titration was pH 4.0, and the end point was reached near pH 8. Total volumes of 75 or 100 cc were used for the titrations, and the ionic strength was controlled at 0.01 M NaCl. 

S. Scaccia and M. Carewska, Determination of Stoichiometry of Li, +)Co02 Materials by Flame Atomic Absorption Spectrometry and Automated Potentiometric Titration, Anal. Chim. Acta 2002,453, 35. 

Potentiometric titration curves normally are represented by a plot of the indicator-electrode potential as a function of volume of titrant, as indicated in Fig. 4.2. However, there are some advantages if the data are plotted as the first derivative of the indicator potential with respect to volume of titrant (or even as the second derivative). Such titration curves also are indicated in Figure 4.2, and illustrate that a more definite endpoint indication is provided by both differential curves than by the integrated form of the titration curve. Furthermore, titration by repetitive constant-volume increments allows the endpoint to be determined without a plot of the titration curve the endpoint coincides with the condition when the differential potentiometric response per volume increment is a maximum. Likewise, the endpoint can be determined by using the second derivative the latter has distinct advantages in that there is some indication of the approach of the endpoint as the second derivative approaches a positive maximum just prior to the equivalence point before passing through zero. Such a second-derivative response is particularly attractive for automated titration systems that stop at the equivalence point. 

NaCl solution. In one set of experiments, the slurry was titrated with 0.1 normal NaOH solution in one cm increments to a pH of about 10. The samples of this set are referred to as the "slurry" samples (titration of the calcined zeolite - NaCl solution slurry). In another set of experiments, the calcined zeolite - NaCl solution slurry was filtered, the filter cake washed with about 100 cnP distilled water, and the combined filtrates were titrated with 0.1 N NaOH solution, again to a pH of about 10. The samples of this latter set are referred to as the "filtrate" samples (the zeolite being removed by filtration prior to titration of the filtrate). In addition to the manual titrations, automated potentiometric titration curves were obtained with a Metrohm E636 Titroprocessor, which has an estimated pH measurement accuracy of 0.001 pH unit and an estimated volumetric addition accuracy of 0.001 cm ... 

The monitoring system based on the potentiometric titration of resin-bound unreacted amino groups 29,30) has helped the development of much advanced fully automated peptide synthesizers 37,38). This computarized system evaluates automatically the synthetic data and decides whether to proceed to the next step, to repeat the last step, or to stop the synthesis. Very recently Edelstein et al.391 designed and im-... 

Acoustic methods offer several advantages when compared to other comparable techniques (1) applicable to concentrated suspensions (2) less sensitive to particulate contamination (3) better suited to polydisperse suspensions (4) applicable to a wide size range (5) well suited to automated potentiometric titrations and analysis... 

The determination of ascorbic acid in foods is based, in part, on its ability to be oxidized or to act as a reducing agent. The most common method for determination of vitamin C in foods is the visual titration of the reduced form with 2,6-dichloroindophenol (DCIP) (4-7). Variations in this procedure include the use of a potentiometric titration (6), or a photometric adaptation (S) to reduce the diflSculty of visually determining the endpoint in a colored extract. The major criticisms of this technique are that only the reduced vitamin, and not the total vitamin C content of the food, is measured, and that there can be interference from other reducing agents, such as sulfhydryl compounds, reductones, and reduced metals (Fe, Sn, Cu), often present in foods. The DCIP assay can be modified to minimize the effects of the interfering basic substances, but the measurement is still only of the reduced form. Egberg et al. (9) adapted the photometric DCIP assay to an automated procedure for continuous analysis of vitamin C in food extracts. 

In titrimetric methods, LPS catalyzes the hydrolysis of fatty acids from an emulsion of olive oil or oleic acid. The fatty acids liberated are titrated with dilute allcali. Kinetic versions use an automated potentiometric titrator (an instrument commonly referred to as a "pH-stat ). The amount of aUcah used is recorded as a function of time and serves as a measure of fatty acid produced during the reaction. This method has been proposed as reference measurement procedure, useful in the evaluation of new LPS methods. ... 

Potentiometric titrations provide data that are more reliable than data from titrations that use chemical indicators, and they are particularly useful with colored or turbid. solutions and for detecting the presence of unsuspected species. Potentiometric titrations have been automated in a variety of different ways, and commercial titrators are available from a number of manufacturers. Manual potentiometric titrations, however, suffer from the disadvantage of being more time consuming than those involving indicators. 

Avdeef (1998) has reported an automated potentiometric titration method for the determination of solubilities of drug substances containing ionizable groups, where a graphical procedure is used for the estimation of solubility constants based on Bjerrum difference plots. One useful relation derived in this work was ... 

Martinez V, Maguregui MI, Jimenez RM, Alonso RM. Determination of the pKa values of beta-blockers by automated potentiometric titrations. J Pharm Biomed Anal 2000, 15 Aug 23(2-3) 459-468. 

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. 

Potentiometric titrations can be easily automated and controlled by microprocessors or computers. The extent of automation is such that, in the same vessel, multiple titrants may be used sequentially, providing for the determination of several analytes in one sample. Sample changers carrying up to and beyond 60 samples can be attached with ease, vastly decreasing the technician time to produce multiple sample results. 

Analytical estimation of Cl in soil suspensions can be performed (following filtration or centrifugation) by potentiometric titration, automatic colorimetric analysis (automated ferricyanide method) and ion chromatography. Choice of... 

A difficulty in the use of glass pH electrodes, even in aqueous solutions, but especially in partly aqueous solutions, is that they are relatively slow to respond to changes in hydronium ion activity. Equilibration times of at least 1 min are generally needed for each data point in a titration that might have a total of more than 20 points. This has two consequences (a) potentiometric titrations are relatively time consuming and thus (b) workers can become too impatient to wait for the electrode response to fully stabilize, leading to further measurement errors. Automated measurement, such as with Sirius autotitration equipment, is able to measure about 25 pKa values per day. Faster alternatives to the pH electrode are needed to rapidly measure pKa values. 

An automated potentiometric titration method has been described for iV-(phosphonomethyl) iminodiacetic acid and a theoretical method has been developed to successfully predict the oxidation potentials of a number of amines and thus a range of organophosphorus compounds in CH3CN... 

The most important component of an automated potentiometric titrator is the potentiometer. In simpler titrimeters, ordinary burettes are used to deliver the titrant and are equipped with automatic valves. Usually piston (syringe) burettes that allow delivery of the titrant with predetermined constant or variable speed are employed. Most automatic titrators have built-in electronic switches to perform various duties and include one or more derivatizing circuits enabling the location of the endpoint. The automated potentiometric titrators available in the market may be divided into four groups (1) automatic titration curve recording instruments (2) preset endpoint titrators, in which the flow of the titrant is stopped when the potential of the indicator electrode reaches a preselected value (3) first- or... 

A simple potentiometric method for the determination of silica in solutions of alkali metal silicates is described. The precision of the determination of Na20 and SiQz in silicates was improved and the determination time decreased by developing a potentiometric titration method. Better determination results due to potentiometric detection of the endpoint pH are demonstrated by comparison with gravimetric determination of Na20 and Si02 in water glass containing 26-260 g/L. The potentiometric determination method can be easily automated. 

An automated version of potentiometric titration can be used with flow injection analysis. In this application, termed pseudotitration (138), the mobile phase of the flow injection analysis system contains a constant concentration of the titrant, which can be either an anionic or cationic surfactant. The sample, containing either a cationic or anionic surfactant, is passed through an exponential dilution chamber prior to mixing with the mobile... 

Glomme, A., Marz, J., Dressman, J. B. Comparison of a miniaturized shake-flask solubility method with automated potentiometric acid/base titrations and calculated solubilities. /. Pharm. Set. 2005, 94, 1-15. 

Lebel [224] has described an automated chelometric method for the determination of sulfate in seawater. This method utilises the potentiometric end-point method for back titration of excess barium against EDTA following precipitation of sulfate as barium sulfate. An amalgamated silver electrode was used in conjunction with a calomel reference electrode in an automatic titration assembly consisting of a 2.5 ml autoburette and a pH meter coupled to a recorder. Recovery of added sulfate was between 99 and 101%, and standard deviations of successive analyses were less than 0.5 of the mean. 

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