POTENTIOMETRY

Pharmaceutical Chemistry
GES’s Sir Dr. M. S. Gosavi College of
Pharmaceutical Education and Research, Nashik.
By : Ms. Rucha S. Dadke
Date: 25/04/2021

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 Glass electrode for pH measurement-
• The Composition and Structure of Glass Membranes- Glass composition
affects the sensitivity of membranes to protons and other cations – Corning
glass, which has been widely used for membranes, consists of
approximately 22% Na2O, 6% CaO, and 72% Si02.
• This membrane is specific in its response toward hydrogen ions up to a pH
of about 9. At higher pH values, however, the glass becomes somewhat
responsive to sodium, as well as to other singly charged cations .
• Other glass formulations are now in use in which sodium and calcium ions
are replaced to various degrees by barium and lithium ions. These
membranes have superior selectivity at high pH.
• Cross-sectional view of a silicate glass membrane structure. Each silicon
atom is shown as being bonded to three oxygen atoms in the plane of the
paper. In addition, each is bonded to another oxygen above or below the
plane.

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The Composition and Structure of Glass Membranes

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 Glass electrode for pH measurement-
• Thus, the glass consists of an infinite three-dimensional network of SiO, -
groups in which each silicon is bonded to oxygens and each oxygen is
shared by two silicons. Within the interstices of this structure are sufficient
cations to balance the negative charge of the silicate groups.
• Singly charged cations, such as sodium and lithium, are mobile in the
lattice and are responsible for electrical conduction within the membrane.
• The Hygroscopicity of Glass Membranes -The surface of a glass
membrane must be hydrated before it will function as a pH electrode.
• Nonhygroscopic glasses show no pH function. Even hygroscopic glasses
lose their pH sensitivity after dehydration by storage over a desiccant.
• The effect is reversible, however, and the response of a glass electrode can
be restored by soaking it in water.
• The hydration of a pH-sensitive glass membrane involves an ion-exchange
reaction between singly charged cations in the interstices of the glass lattice
and protons from the solution.

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• The equilibrium constant for this process is so large that the surface of
a hydrated glass membrane ordinarily consists entirely of silicic acid (H
+GI-) groups.
• Electrical conduction -To serve as an indicator for cations, a glass
membrane must conduct electricity. Conduction within the hydrated gel
layer involves the movement of hydrogen ions. Sodium ions are the
charge carriers in the dry interior of the membrane. Conduction across
the solution-gel interfaces occurs by the reactions H+ + Gl-  H+G.

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pH is determined by formation of boundary potential across glass
membrane
• Whenever there is a charge imbalance across any material, there is an
electrical potential across the material: – the concentration of protons
inside the membrane is constant, and the concentration outside is
determined by the concentration, or activity, of the protons in the
analyte solution.
• This concentration difference produces the potential difference that we
measure with a pH meter.
• At each membrane-solvent interface, a small local potential develops
due to the preferential adsorption of H+ onto the glass surface.

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pH is determined by formation of boundary potential
across glass membrane

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 Cell potentials-
• The cell potential of an electrochemical cell is the potential
difference occurring between the two electrodes of the cell, and
arises due to the transfer of electrons through the external circuit of
a cell that has not reached equilibrium. This is related to the Gibbs
free energy change for the cell reaction given by:
• ΔG=−nEcellF
• where ∆G = Gibbs free energy change (J), n = number of electrons
transferred per unit overall reaction (mol), Ecell = cell potential
(V), F = Faraday constant (96485.33 C mol− 1). (F= magnitude of
electric charge per moles of electrons)
• Furthermore, the cell potential is related to the composition of the
reaction mixture via the Nernst Equation:

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 Cell Potentials
• The potentials of the two reference electrodes – depend on the
electrochemical characteristics of their respective redox couples.
• The potential across the glass membrane: – depends on the
physicochemical characteristics of the glass and its response to ionic
concentrations on both sides of the membrane.
• 4 potentials: – EAg, AgCl and ESCE, are reference electrode potentials
that are constant. – A 3rd potential is the junction potential Ej across the
salt bridge that separates the calomel electrode from the analyte
solution. – The 4th and most important potential is the boundary
potential, Eb , which varies with the pH of the analyte solution. pH is
determined by formation of boundary potential across glass membrane.
• Boundary Potential- The resulting difference in potential between the two
surfaces of the glass is the boundary potential, which is related to the
activities of hydrogen ion in each of the solutions by the Nernst-like
equation.

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• The Asymmetry Potential- When identical solutions are placed on the two
sides of a glass membrane, the boundary potential should in principle be
zero. In fact, however we frequently encounter a small asymmetry potential
that changes gradually with time due to slight imperfections in the
membrane The Asymmetry Potential.
• The sources of the asymmetry potential are obscure but undoubtedly
include such causes as differences in strain on the two surfaces of the
membrane created during manufacture, mechanical abrasion on the outer
surface during use, and chemical etching of the outer surface.
• To eliminate the bias caused by the asymmetry potential, all membrane
electrodes must be calibrated against one or more standard analyte
solutions.
• Such calibrations should be carried out at least daily, and more often when
the electrode receives heavy use.
• The potential of a glass indicator electrode Eind has three components:
• The boundary potential,
• The potential of the internal Ag/AgCl reference electrode.
• The small asymmetry potential which changes slowly with time.

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 Instruments for measuring cell potential-
• Most cells containing a membrane electrode have very high electrical
resistance. 100 M Ω or more, In order to measure potentials of such high-
resistance circuits accurately, it is necessary that the voltmeter have an
electrical resistance that is several orders of magnitude greater than the
resistance of the cell being measured. ( at least 1012 Ω.) If the meter
resistance is too low, current is drawn from the cell, which has the effect of
lowering its output potential (IR drop), thus creating a negative loading error.
• From Ohm's law, we may write Es = IRs + IRm, I is the current in this circuit
consisting of the cell and the measuring device . The current is then given by,
I= 0.8 / (20+100)x106 Ω = 6.67 x 10 -9 A
The potential drop across the measuring device,
Em = (6.67x10-9 A ) x (100 x 106 Ω ) = 0.667 V
Relative error: ( 0.667 V – 0.8 V ) / 0.8 V x100%= - 17 %

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• We can easily show that to reduce the loading error to 1%, the
resistance of the voltage measuring device must be about 100 times
greater than the cell resistance; for a relative error of 0.1%, the
resistance must be 1000 times greater.
• Numerous high-resistance, direct-reading digital voltmeters with
internal resistances of >10₁₁ ohms called pH meters or pIon meters
or ion meters are available.
• Direct potentiometric measurements- Direct potentiometric
measurements provide a rapid and convenient method for determining the
activity of a variety of cations and anions. The technique requires only a
comparison of the potential developed in a cell containing the indicator
electrode in the analyte solution with its potential when immersed in one or
more standard solutions of known analyte concentration.

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• Substitution and rearrangement leads to The constant terms can be
combined to give a new constant K, For an anion A. When the two
equations are solved for Ecell, we find that for cations and anions is
governed by the equation given.
• Equations Governing Direct Potentiometry- For direct potentiometric
measurements, the potential of a cell can then be expressed in terms of the
potentials developed by the indicator electrode, the reference electrode, and
a junction potential,
• Ecell = Eind – Eref + Ej For the cation Xn+ at 25°C, the electrode response
takes the general Nernstian form Eind= L-(0.0592/n)px = L+(0.0592/n)log
ax.

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• Commercial Instrumments-
• . The range of plon meters based on price and readability. We can classify
four groups of 1 including utility meters, which are portable, usually
battery-operated instruments that are intended for the consumer market and
are about the size of a digital medical thermometer.
• Generally utility meters can resolve about 0.5 pH unit or better.
• General-purpose meters are line-operated instruments, which can measure
pH up to 0.05 pH unit or better.
• The thermistor or thermocouple may also be incorporated to merely
analyze the temperature or as a probe to be immersed in the anayte
solution.
• Many offer such features as digital readout, automatic temperature
compensation (ATC), scale expansions so that full scale covers 1.4 units
instead of 0 to 14 units, and a millivolt scale. Expanded-scale instruments
are generally readable to 0.01 pH unit or better.

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• Most offer full-scale ranges of 0.5 to 2 pH units (as well as 0-to-7 and 0 to-
14 ranges), four-digit readout, push-button control, millivolt scale, and
automatic temperature compensation.
• Research meters are readable to 0.001 pH unit or better, generally have a
five-digit display. Note that the readability of these instruments is usually
significantly better than the sensitivity of most selective electrodes.
• The ATC feature in many commercial instruments usually consists of a
thermistor or thermocouple and associated circuitry that provide a signal
proportional to temperature.
• This signal is then used to correct the output by adjusting the slope of
transfer function of the instrument (2.303RT/F=UD92 at 25°C) using either
software calculation or analog circuitry.

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• Figure gives the response of a liquid-membrane electrode to variations in
the concentration and activity of calcium ion. The nonlinearity is due to the
increase in ionic strength—and the consequent decrease in the activity of
calcium ion—with increasing electrolyte concentration.
• The electrode-calibration method is also referred to as the method of
external standards (Quantitative method). The electrode-calibration method
offers the advantages of simplicity, speed, and applicability to the
continuous monitoring of pX or pA. However, there is an inherent error (of
the order of ≥1 mV) in the electrode calibration method that results from
the assumption that K remains constant after calibration.
• Activity versus Concentration

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Potentiometric pH Measurement with
the Glass Electrode
• The glass/calomel electrode system is a remarkably versatile tool for
the measurement of pH under many conditions. However, there are
distinct limitations to the electrode:
• 1. The alkaline error
• 2. The acid error
• 3. Dehydration
• 4. Errors in low ionic strength solutions
• 5. Variation in junction potential
• 6. Error in the pH of the standard buffer
• 7. Errors resulting from temperature changes.

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• Standard-Addition Method- The standard- addition method, is equally
applicable to potentiometric determinations. In this method, the potential of the
electrode system is measured before and after addition of a small volume (or
volumes) of a standard to a known volume of the sample.
The standard-addition method has been applied to the determination of chloride
and fluoride in samples of commercial phosphors, In this application, solid state
indicator electrodes for chloride and fluoride were used in conjunction with a
reference electrode: the added standard contained known quantities of the two
anions.
• The relative standard deviation for the measurement of replicate standard samples
was 0.7% for fluoride and 0.4% for chloride. In routine use with
real samples, the standard-addition method yielded relative standard deviations of
1.1% for fluoride and 0.8% for chloride.
• Quantitative Analysis Using External Standards-For the determination of the
concentration of an analyte in a sample, it is necessary to standardize
the electrode.
• If the electrode’s response obeys the Nernst equation, then only the constant K nee
d be determined and standardizing with a single external standard is possible.
Since small deviations from the ideal ―Nerstian‖ slope of ±RT/nF or ±RT/zF are
frequently observed, standardization is usually accomplished using two or more ex
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-ternal standards.
• In most quantitative analyses we are interested in determining the concentrat
ion, not the activity of the analyte. As noted earlier, however, the electrode’s
response is a function of the analyte’s activity. In the absence of interferents,
a calibration curve of potential versus activity is a straight line. A plot of pot
ential versus concentration, however, may be curved at higher concentration
s of analyte due to changes in the analyte’s activity coefficient.
• A curved calibration curve may still be used to determine the analyte’s conce
ntration if the standard’s matrix matches that of the sample. When the exact
composition of the sample matrix is unknown, which often is the case, matri
x matching becomes impossible.
• Another approach to matrix matching, which does not rely on knowing the e
xact composition of the sample’s matrix, is to add a high concentration of in
ert electrolyte to all samples and standards.
• If the concentration of added electrolyte is sufficient, any difference between
the sample’s matrix and that of the standards becomes trivial, and
the activity coefficient remains essentially constant.
• The solution of inert electrolyte added to the sample and standards is called a
total ionic strength adjustment buffer (TISAB).
•

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 Summary of Errors Affecting pH
Measurements with glass electrode-
• The ubiquity of the pH meter & the general applications of the glass
electrode tend to hypothesis that any measurement is surely correct
obtained with it. It is however a good suggestion to guard against this false
sense of security because there are distinct limitations to the electrode
system. They are as follows;
1. The alkaline error- Modern glass electrodes become somewhat sensitive
to alkali-metal ions at pH values greater than 11 to 12.
2. The acid error- At a pH less than 0.5, values obtained with a glass
electrode tend to be somewhat high.
3. Dehydration- Dehydration of the electrode may cause unstable
performance errors.
4. Error in the pH of the standard buffer. Any inaccuracies in the
preparation of the buffer used for calibration, or changes in its
composition during storage, are propagated as errors in pH measurements.
A common cause of deterioration is the action of bacteria on organic
components of buffers.
•

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5. Errors in low-ionic-strength solutions. Significant errors (as much as 1
or 2 pH units) may occur when the pH of low-ionic-strength samples, such
as lake or stream samples, are measured with a glass electrode from partial
clogging of the fritted plug or porous system. The prime source of such
errors is nonreproducible junction potentials, which result from partial
clogging of the fritted plug or porous fiber that is used to restrict the flow
of liquid from the salt bridge into the analyte solution. To over-come this
problem, free diffusion junctions of various types have been designed, and
one is produced commercially. In the commercial junction, an electrolyte
solution is dispensed from a syringe cartridge through a capillary tube, the
tip of which is in contact with the sample solution. Before each
measurement, 6 uL of electrolyte is dispensed so that a fresh portion of
electrolyte is in contact with the analyte solution.
6. Errors resulting from temperature changes. When pH measurements
are made at temperatures other than 25°C, pH meters must be adjusted to
compensate for the change in the nernstian response of the glass electrode.
Compensation is often accomplished with ATC circuitry or software in
modern meters, but with older meters, manual adjustment of the slope (or
temperature) control may be necessary.

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7. Variation in junction potential- to re-emphasize that variation in the
junction potential between standard and sample leads to a fundamental
uncertainty in the measurement of pH that is not correctable. Absolute
measurements more reliable than 0.01 pH unit are generally unobtainable,
Even reliability to 0.03 pH unit requires tremendous care. On the other
hand, it is often possible to detect pH differences between similar
solutions or pH changes in a single solution that are as small as 0.001 unit.
For this reason, many pH meters are designed to produce readings to less
than 0.01 pH unit and can minimize the variation in the junction potential.

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• The Operational Definition of pH-
• The utility of pH as a measure of the acidity or alkalinity of aqueous media,
the wide availability of commercial glass electrodes, and the proliferation
of inexpensive solid-state pH meters have made the potentiometric
measurement of pH one of the most common analytical techniques in all of
science. It is thus extremely important that pH be defined in a manner that
is easily duplicated at various times and various laboratories throughout the
world. To meet this requirement, it is necessary to define pH in operational
terms - that is, by the way the measurement is made. Only then will the pH
measured by one worker be the same as that measured by another.
• The operational definition of pH endorsed by the National Institute of
Standards and Technology (NIST), similar organizations in other countries,
and the International Union of Pure and Applied Chemistry (IUPAC) is
based on the direct calibration of the meter with carefully prescribed
standard buffers followed by potentiometric determination of the pH of
unknown solutions.

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• Consider, for example, the glass-reference systems in the given Figure.
When these electrodes are immersed in a standard buffer at 25°C, Equation
applies and we can write
pHs= -(Es- K/ 0.0592)
Where,
Es is the cell potential when the electrodes are immersed in the standard buffer.
Similarly, if the cell potential is Eu when the electrodes are immersed in a
solution of unknown pH also at 25°C, we have

pHu =( Eu- K)/0.0592 24

pHu= pHs – (Eu – Es)/ 0.0592

• Equation has been adopted throughout the world as the

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• pH measurement in non-aqueous and mixed solutions- poses a number of
issues such as dissociation of the solvent, different pH scale, and liquid junction potential
to name a few. The typical problems encountered during measurement with pH electrodes
are slow response time, unstable readings, and erroneous results. As non-aqueous solvents
have very low conductivity and can dehydrate the glass membrane, it is difficult to use
glass electrodes in measuring pH directly. There must be some electrical conductivity
through the solution and glass membrane must be hydrated to function well.
• For water-immiscible non-aqueous solvents and non-aqueous solutions with water-
immiscible solvents, this measurement can be accomplished by adding water as described
in the method above. Pure water with very low buffering capacity and no dissolved salts
should be mixed thoroughly with the solvent. Once the two phases are in equilibrium with
each other, the activity of any dissolved species should be the same in both phases.
• After separating the solvent phase, the pH of water phase is then measured. For water-
miscible non-aqueous solvents and mixed aqueous/water-miscible non-aqueous solutions
(e.g., water and methanol), a reproducible measurement process can be achieved if the
solvent background is known and constant. To do this, it is important to describe the
choice of pH electrode, calibration standards, sample preparation, and electrode
conditioning.
• The electrode should have an adequate outward flow from the junction and the junction
design should permit easy cleaning for optimum performance. These two key features
prevent memory effects at the junction and minimize liquid junction potential.
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• 1. pH electrode- A glass-body electrode resists chemical attack. A flowing
reference should be used to eliminate or minimize liquid junction problem. An
aqueous filling solution may be used, but most often develops a large or unstable
junction potential. This can be reduced by changing the filling solution so that it is
compatible with the sample (e.g., methanol saturated with KCl, 90% glacial acetic
acid plus 10% saturated aqueous LiCl).
• 2. Calibration Standards- Ideally, the calibration standards should have the same
background as the sample. A constant solvent background may be used in testing
the measuring system. A ―check‖ standard made with dry buffer and same solvent
background can be measured after calibrating the electrode/meter system in
aqueous pH buffers. Its reproducibility is a good test although the reading will be
different from the aqueous values. In pH measurement of non-aqueous and mixed
solutions, only relative readings can be obtained.
• 3. Sample Preparation- The ionic strength of non-aqueous solvents can be
increased by adding a neutral electrolyte such as a quarternary ammonium salt.
• 4. Electrode Conditioning- When measuring pure solvents or samples with less
than 20% water, the contact time of the electrode to the sample should be kept to a
minimum as solvents may dehydrate the glass membrane. Between measurements
and after use, it should be soaked in buffer or KCl solution to hydrate the glass
membrane. Dried electrodes can be drifty and sluggish.
• To obtain accurate results, standard buffer solutions and samples should be
measured at the same temperature. If the electrode is coated with oily material from
a sample, clean it with detergent and warm water. 27
THANK YOU.

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