Titration Point Research Articles

Defining the role for gabapentin in the treatment of trigeminal neuralgia: A retrospective study

The preferred treatment for trigeminal neuralgia consists of antiepileptic drugs. Among them, gabapentin has shown promise in relieving some forms of neuropathic pain. This retrospective review examined 194 consecutive cases of trigeminal neuralgia, many of whom had paroxysmal facial pain resistant to previous surgical interventions or treatment with multiple medications. Of the 92 who had received a trial of gabapentin, 43 reported reduction in facial pain. This benefit was complete in 16, nearly complete in 9, moderate in 12, and partial in 6. Onset of pain relief occurred generally within 1 to 3 weeks, depending on the rate and end point of dose titration. The effective range of stable daily dosing varied from 100 to 2400 mg divided 3 times a day, with a mean of 930 mg. Pain relief was sustained in two thirds during a mean follow-up time of 8 months. The fact that gabapentin was well-tolerated and without serious side effects is an important advantage when prescribing for elderly patients. The present study suggests that gabapentin can be effective as first or second line treatment of trigeminal neuralgia, even in cases resistant to traditional treatment modalities. © 2002 by the American Pain Society

Calcium binding to proteins studied via competition with chromophoric chelators.

Optical spectroscopic techniques can be used to measure Ca2+-binding constants when the Ca2+-bound and free forms of the protein display a difference in, for example, the UV absorbance, CD or fluorescence spectrum, or fluorescence polarization. One may then start with the Ca2+-free form, titrate in Ca2+ stepwise, measure a spectrum or intensity at each step, and obtain the binding constants from computer fitting to the data. The best accuracy is achieved when the protein concentration is roughly the same as the dissociation constant (the inverse of the binding constant) such that there are significant populations of both bound and free forms at several titration points. This limits the useful range of such direct measurements to binding constants below 106 M-1 (KD> 1 μM), because of the practical difficulty of making buffers with less than 0.5-1 μM free Ca2+. For Ca2+-binding proteins with affinities of 106 M-1 and up, one has to rely on indirect measurements. One popular such approach uses around 1 mM ethylenediaminetetracetic acid (EDTA) or ethylene glycol-bis N,N,N′,N′-tetraacetic acid (EGTA), and a much smaller amount of protein so that the free-Ca2+concentration is essentially controlled by the Ca2+-buffering capacity of EDTA or EGTA. A potential risk with such approaches is binding of EDTA or EGTA to the protein with consequences for its Ca2+affinity. Another type of indirect approach outlined in this chapter involves the use of a chelator whose absorbance or fluorescence is Ca2+dependent (1-3).

Stoichiometric redox titrations of complex metalloenzymes

This chapter describes stoichiometric redox titration method and points out difficulties and avoidable pitfalls. This method may provide reliable evidence for a spectroscopically silent redox center in an enzyme, as long as the reduction potential of the center is within the potential range probed. Such centers may consume redox equivalents and thus alter the shape of the titration curves of spectroscopically active centers. Spectroscopically observable stable redox states are commonly viewed as being more important than those which cannot be easily observed, but this need not be the case. Thus, the results of stoichiometric titration studies may be critical for formulating the correct mechanism of catalysis. Finally, despite best efforts, some uncertainty in the results and analysis will inevitably remain. This ultimately translates into some persistent uncertainty regarding the redox/spectroscopic system present in the enzyme.

Characterization of Acid Catalysts by Thermometric Titration

Thermometric titration as a method suitable for the characterization of the acidity of catalysts is presented. The determination of the acid strength, the end point of titration and the total heat of neutralization by thermometric titration is tested using samples of benzoic acid, zeolite NaHY and unsupported and supported (TiO2, SiO2, SiO2· Al2O3) tungstosilicic acid. The determination of the end point of titration acidity is discussed. The method is recommended for the determination of the total neutralization enthalpy as well as the enthalpy of the neutralization of the strongest acid centers in solid catalysts.

Complexometric determination, Part II: Complexometric determination of Cu2+-ions

A copper-selective electrode of the coated wire type based on sulphidized copper wire was applied successfully for determining Cu(II) ions by complexometric titration with the disodium salt of EDTA (complexon III). By the formation of internal complex compounds with the Cu(II) ion, the copper concentration in the solution decreases, and all this is followed by a change of potential of the indicator system Cu-DWISE (or Cu-EDWISE)/SCE. At the terminal point of titration, when all the Cu(II) ions are already utilized for the formation of the complex with EDTA, there occurs a steep rise of potential, thus enabling us, through the first or second derivative to note the quantity of copper that is present in the solution. Copper-selective electrode showed a responsivity towards titration with EDTA as a complexing agent, with the absence of "fatigue" due to a great number of repeated measurings. Errors occurring during quantitative measurements were more a characteristic of the overall procedure which involve, because of the impossibility of the complete absence of subjectivity, a constant error, and the reproducibility of the results confirmed this fact. The disodium salt of EDTA appeared as a very efficient titrant in all titrations and with various concentrations ot Cu(II) ions in the solution, with somewhat weaker response at lower concentrations in the solution.

Measurement of pH, alkalinity and acidity in ultra-soft waters

Conventional characterisation of low alkalinity waters via pH measurement and titration of total alkalinity to a prescribed end-point invariably leads to large errors. These errors result from instability of the pH probe and an unknown titration end-point. In this paper two indirect methods (termed the "double Gran function" and the "blend" method) for the characterisation of such waters are evaluated critically. A blend composed of the raw water, sodium chloride (to increase conductivity), and standard bicarbonate (to increase buffering capacity) was titrated with standard strong acid in two pH regions: 6.3 < pH < 7.0, and 3.5 > pH < 4.0. In both methods, total alkalinity was determined using the latter set of points, and the first Gran function. In the double Gran function method the upper set of titration points was used to determine CO2 acidity using the second Gran Function. In the "blend" method, equilibrium chemistry data were used to calculate total acidity for each point based on the known total alkalinity, pH reading, temperature and ionic strength. The two methods gave excellent results (in terms of both repetition and accuracy) as compared to characterisation based on total alkalinity and inorganic carbon analysis. A detailed procedure for the execution of the two approaches is given in an appendix. WaterSA Vol.27(4) 2001: 423-432

Data analysis in the chemical laboratory: II. The end-point estimation in instrumental titrations by nonlinear regression

The regression model for a two-segments titration curve with a break-point at the end-point is analyzed. Both linear and nonlinear shapes of the titration curve segments are treated. An effective and simple method discriminates which of two segments is linear or curved. The point and interval estimates of the end-point are calculated by the nonlinear least squares of curve fitting technique. The nonlinear regression method is applied to any, linear or nonlinear, type of a two-segments titration curve without excluding any titration points to reach the most probable point estimate of the end-point together with its 100(1− α)% confidence interval. An accuracy and precision of the proposed end-point estimation is examined on several instrumental titrations. A sample program in S-Plus™ is provided.

Determination of Na 2O from sodium aluminate NaAlO 2

The aim of the work was to find a suitable method and conditions for determining Na 2O wt.% from NaAlO 2. Problems were encountered while titrating NaAlO 2 with hydrochloric acid. The problematic area was the pH range 4–10 where aluminum precipitates as hydroxides. The different species of the aluminate solution were determined using potentiometric and complexometric titrations. The equivalent point of the potentiometric titration was detected using Gran's plotting method. Precipitation of aluminum hydroxides did not interfere with titrations, because in potentiometric titrations the pH value was over 10 and in complexometric titrations the pH was 4. The results were accurate and determinations were easy to carry out. Sodium was also determined by DCP-AES.

Precipitation of lead sulfide for surface chemical studies

Although there seems to be a general agreement that the surface chemical properties of precipitated lead sulfide depend on the surface stoichiometry of the precipitate, the effect of the precipitation conditions on the surface stoichiometry has not been studied in detail. In this work, the precipitation procedure, per se, was studied by titrations with lead nitrate and sodium sulfide solutions. The titrations were controlled potentiometrically using glass, redox, and ion-selective (Pb 2+, S 2−) electrodes and supplemented by analyses of the precipitates. It was found that the titration speed exercised a major influence upon the results. When the titrations of lead nitrate solutions with sodium sulfide solutions were conducted slowly enough, two inflection points and slow achievement of equilibria at the titration points between them were obtained and were explained as being due to lead and sulfide ions adsorbing on the surfaces of the final crystals. Further, the position of the major inflection point was found to depend on the titration speed, which was explained by considering the coprecipitation of nitrate ions with lead sulfide. The coprecipitation was verified by analyzing the precipitates, which were shown to contain up to 3% nitrate. Due to these coprecipitation and adsorption phenomena, the addition of an equivalent amount of sulfide to a lead nitrate solution results in a lead sulfide suspension bearing an excess of sulfide on the surfaces. Both in situ monitoring of the precipitation by ion-selective electrodes and facilitated desorption of the excess adsorbed sulfide ions at a correctly adjusted pH are suggested as better methods for producing lead sulfide suspensions.

Electrochemical studies of complexation of Pb in red wines

Ion-selective electrode potentiometry and cathodic voltammetric techniques were used to study the Pb complexometric properties of four monovarietal wines, ‘Touriga Nacional’ (TN), ‘Touriga Francesa’ (TF), ‘Tinta Roriz’ (TR) and ‘Tinta Barroca’ (TB). The data from titrations of the samples with a Pb solution were treated by two methods suitable for systems involving polymeric heterogeneous ligands: (1) the Scatchard plot, which provided the total complexation capacity of the sample (CCtotal) and average conditional stability constants (Kav), and (2) the differential equilibrium function (DEF), which provided values for differential conditional stability constants (KDEF) as a function of the titration point. The CCtotal of the wines ranged between 4.5 × 10−3 M (TF) and 1.0 × 10−2 M (TN). Potentiometric titrations provided values of log(|Pb|bound/CCtotal) = log θ between 0.015 and 0.45, and the respective log Kav between 5.6 (TF) (log KDEF between 4.7 and 5.5) and 3.0 (TR) (log KDEF between 2.8 and 3.7). Cathodic voltammetry, carried out only for TR and TN, provided the concentrations of only the strongest ligands of the wines (i.e. those that are operationally inert), which were 27 μM (TR) and 43 μM (TN), and two different log Kav for TN, 7.6 and 6.6, and only one, 7.2, for TR, for log θ 0.0025–0.015 (TN) and 0.0014–0.0075 (TR). Since the values of log θ in wines are lower than those embraced in the experiments, this study indicates that Pb is strongly complexed in wines. Therefore, a low bioavailability of Pb can be expected.

A novel and simple method for determining the cationic demand of suspensions using chromophoric labeled cationic polymers

A cationic demand (CD) is a very useful indication for determining the optimum dosage rate of cationic flocculants to the suspensions. Polyelectrolyte titration has been most often used to determine a CD. This method works very well when the ionic strength of sample is low, but is accompanied by the serious errors when the ionic strength is higher than that corresponding to 20 mM monovalent, 2 mM divalent, or 0.2 mM trivalent ions because of no occurence of the end point of titration. Therefore, it is difficult for the conventional method to be applied to the industrial suspensions such as papermaking stock and industrial waste water. Therefore, a novel method using chromophoric-labeled cationic polymer which can be applicable to the sample with high ionic strength has been developed.

Role of polyphenols in copper complexation in red wines.

Four monovarietal red wines, Tinta Roriz, Tinta Barroca, Touriga Nacional, and Touriga Francesa, were studied for their complexometric properties toward copper. For the purpose, ion selective electrode potentiometric titrations were carried out, and the data were treated by two methods suitable for heterogeneous ligands: the Scatchard plot, which provided the complexation capacity (CC(total) = maximum number of moles of sites per liter), and the differential equilibrium function (DEF), which provided the conditional stability constants of the sites effectively involved in the metal complexation (K(DEF)) at a given titration point. The different wines displayed similar properties: CC(total) ranged from 4.5x10(-3) (Tinta Barroca) to 4.9x10(-3) M (Touriga Francesa), and log K(DEF) values were between 4.2 and 6.5. The range of log(|Cu|(bound)/CC(total)) = log theta embraced in the titration was between -0.2 and -1.9. With regard to the natural levels of copper, from 4.4x10(-7) (Tinta Roriz) to 1.3x10(-6) M (Touriga Nacional), and ligands (CC(total)) in the wines, it can be expected that copper will be strongly complexed in the studied wines (log K(DEF) > 6). Studies carried out, in parallel, for solutions of isolated seed tannins and skin polyphenols (mainly anthocyans) showed that their contribution to the CC(total) of the wines was <40% for tannins and <2% for skin polyphenols. However, skin polyphenols were shown to be much stronger copper ligands (log K(DEF) = 6.7, log theta = -1.5) than tannins (log K(DEF) = 4.5, log theta = -1.5).

Determination of the Glass Electrode Parameters by Means of Potentiometric Titration of Acetic Acid in Aqueous Sodium or Potassium Chloride Solutions at 25°C

Single-ion activity coefficient equations are presented for the calculation of stoichiometric (molality scale) dissociation constants Km for acetic acid in aqueous NaCl or KCl solutions at 25°C. These equations are of the Pitzer or Huckel type and apply to the case where the inert electrolyte alone determines the ionic strength of the acetic acid solution considered. Km for a certain ionic strength can be calculated from the thermodynamic dissociation constant Ka by means of the equations for ionic activity coefficients. The data used in the estimation of the parameters for the activity coefficient equations were taken from the literature. In these data were included results of measurements on galvanic cells without a liquid junction (i.e., on cells of the Harned type). Despite the theoretical difficulties associated with the single-ion activity coefficients, Km can be calculated for acetic acid in NaCl or KCl solutions by the Pitzer or Huckel method (the two methods give practically identical Km values) almost within experimental error at least up to ionic strengths of about 1 mol-kg−1. Potentiometric acetic acid titrations with base solutions (NaOH or KOH) were performed in a glass electrode cell at constant ionic strengths adjusted by NaCl or KCl. These titrations were analyzed by equation E = Eo + k(RT/F) ln[m(H+)], where m(H+) is the molality of protons, and E is the electromotive force measured. m(H+) was calculated for each titration point from the volume of the base solution added by using the stoichiometric dissociation constant Km obtained by the Pitzer or Huckel method. During each base titration at a constant ionic strength, Eo and k in this equation were observed to be constants and were determined by linear regression analysis. The use of this equation in the analysis of potentiometric glass electrode data represents an improvement when compared to the common methods in use for two reasons. No activity coefficients are needed and problems associated with liquid junction potentials have been eliminated.

Use of calorimetric titration to determine thermochemical data for interaction of cations with mercapto-modified silica gel

Interactions occurring between mercapto-modified silica gel and silver, mercury, copper and zinc ions in ethanolic solutions have been investigated by using calorimetric titrations with direct determination of the reaction extension. A calorimetric technique is described for the simultaneous determination of thermal effects and quantities of cations that interact at each titration point. From this procedure, values of maximum capacity of interaction ( N s), differential interaction enthalpies at different coverages of the surface (Δ int(i) H m), integral energy of interaction ( Q mon) and molar integral enthalpy of interaction for a monolayer (Δ mon H m) have been obtained. The maximum capacity of interaction values are compared with those previously published for analogous interaction processes in aqueous solutions. Thermochemical quantities are discussed in terms of evaluation criterion of the acid–base interactions, and generally support the conclusion that the Pearson's hypothesis of hard and soft acids and bases is appropriated to describe the behavior of the interaction of the above-mentioned cations.

A fully automated pH–NMR titration set-up for protonation studies

A fully automated pH–NMR titration set-up, consisting of a Bruker 250 MHz NMR instrument and a potentiometric titration unit, has been built so that pH titrations with simultaneous recording of 1H and 31P NMR spectra at each titration point can be run. The new set-up has been tested by studying the protonation of three diazacrown ethers having dangling phosphonate groups. From the fitting of the pH dependences of the chemical shifts of the 31P and 1H signals the protonation constants as well as the chemical shifts of the individual protonated species were obtained using the program HYPNMR. The main advantages of the new set-up are the relatively small amount of substance (0.05 mmol) needed for a single titration and the fact that once started the system needs no operator during the whole titration time (about 20 h).

Determination of Diffuse Double Layer protonation constants for hydrous ferric oxide (HFO): supporting evidence for the Dzombak and Morel compilation

The acid-base properties of hydrous ferric oxide were studied by glass electrode potentiometry. From the Potentiometrie data, surface protonation constants were derived according to the Diffuse Double Layer convention. Chemical equilibrium modelling of the experimental system suggests that titration points below pH 4 should not be used for the determination of protonation constants because of potential HFO dissolution. Surface protonation constant, PZC and binding site estimates agree excellently with currently available best estimates.

Acid–base and copper(II) sorption properties of a natural lake sediment: Potentiometric and atomic absorption spectrometric characterisation

The interactions of the sediment surface with proton and copper(II) ions were investigated by means of alkalimetric titrations performed on suspensions containing different sediment–solution ratios at ionic strengths of 0.1 and 1.0 mol dm −3. As the equilibrium conditions are critical both in acid and in base media for the considered lake sediment, a batch-titration procedure was adopted, which permitted to fully overcome the data uncertainty related to signal drift. Potentiometric data were computed for the refinement of protonation and complexation constants by means of a program, which minimises the difference between calculated and experimental potential values during the refinement. In the elaboration of the potentiometric data some relevant aspects related to the batch-titration procedure were taken into account. As regards the influence of the ionic medium and ionic strength, the experimental data could be refined by assuming that the surface-active centers act independently of one another, without any appreciable effect due to the intervention of the surface charge. The computation showed that all the independent data were consistent and it was possible to refine three protonation constant values, one referring to groups titratable in the acid region and two to groups titratable in the base one. After the determination of protonation constants, copper(II)–sediment interaction was considered: the stability-constant values were calculated by elaborating pH-metric data recorded on the sediment–copper(II) system; copper(II) not adsorbed on the sediment was determined by atomic absorption spectrometry for each titration point; the good agreement between pCu calculated from potentiometric data and measured pCu, by supposing copper(II) mainly bonded to titratable groups, can be considered as a validation of the method.

Rapid, high-precision potentiometric titration of alkalinity in ocean and sediment pore waters

A system for rapid, high precision potentiometric determination of alkalinity in sea water and sediment pore water is presented. Two titration units were used: a 40 ml unit for seawater and a small volume unit for sediment pore water. Titration time was normally less than 10 minutes per sample, including sample exchange. With a 40 ml sample volume, the relative standard deviation of the alkalinity obtained in the laboratory was 0.05% and at sea 0.1 %. The small-volume system (0.5–1.5 ml) gave a precision of 0.07%. Five titration points, in two groups after the second equivalence point, were used to evaluate the equivalence volume. Results from equilibrium calculations and computer simulated alkalinity titrations show that it was possible to use a non-modified Gran function [( V 0 +v) ∗10 ( E Z ) ] and still achieve good accuracy and precision.

Oscillating, nonequilibrium redox properties of humic acids

Humic acids in solution behave as a kinetic system that is characterized by steady-states rather than by equilibria. This is shown by redox measurements at 0.1 M NaCl and 24°C under carefully controlled anaerobic conditions. When the humic acids were titrated with HCl from pH 6.4 to 3, the redox potential, after relaxation to a steady-state, showed a linear pH dependence with a slope of −42 mV/pH unit. (A supplementary study in a 0.1 M NaClO 4 medium, using humic acids prepared from another source, agrees within the limits of experimental errors of ± 1 mV giving a slope of −44 mV/pH unit). In each titration point there was an initial, relatively fast relaxation with a tau-value within the range 150–400 s, followed by further slow relaxation (tau > 2.5 h) and/or oscillations, followed by arrival at a steady-state. This nonequilibrium behaviour implies the presence of polyphenolic residues, such as resorcinol, within the humic acid particles and their free radicals. In a redox diagram, the pH dependence of the apparent redox potential of humic acids is compared with the redox potential of various other redox pairs present in soil.

Potentiometric titration of diprotic systems

The approximate nature of Gran’s method of linearization of potentiometric titration curves applied to diprotic systems has been thoroughly investigated. A function involving pH and titrant volume V (which is linearly dependent on V and becomes zero at the first equivalent point of titration of a weak diprotic base with a strong monoprotic acid) has been critically examined and validated by means of widely extended simulated experiments. Accurate experimental confirmation of the theoretical expressions has been obtained by performing many real titrations of the primary standard Na2CO3 with HCl. This particular application, analytically significant itself, can be a prototype of analogous applications.