Pharmaceutical Analytical Chemistry

Dr. Adel Mohamed Ahmed

 Textbooks
A Textbook of Pharmaceutical Analysis, Kenneth Connors. John Wiley & Sons, New York
Practical Pharmaceutical Chemistry, A.H. Beckell and J.B. Stenlake. The Athione Press, London
Pharmaceutical Drug Analysis, 2nd Ed, Ashutosh Kar, New Age Publications, New Delhi
Fundamentals of Analytical Chemistry, 9th Ed, by Douglas A. Skoog, Donald M. West
Modern Analytical Chemistry, David Harvey, McGraw-Hill

Dr Adel Mohamed Ahmed

 Reference Book
Fundamentals of Analytical Chemistry, 9th Ed, by Douglas A.
Skoog/West/Holler, Saunders Publishing, 2014

Dr Adel Mohamed Ahmed

 Six tips for success in this class
1. actively attending every class and take good notes
2. improving your math (good math is absolutely essential)
3. completing all homework and study textbook, class notes and slides
4. asking questions
5. coming to Dr. Adel’s office hours
6. actively attending every practical class and take good notes

Dr Adel Mohamed Ahmed

1

INTRODUCTION
What is Analytical chemistry?
Analytical chemistry involves the application of a range of techniques and methodologies
to obtain and assess qualitative, quantitative and structural information on the nature of
matter.
● Qualitative analysis is the identification of elements, species and/or compounds present
in a sample.
● Quantitative analysis is the determination of the absolute or relative amounts of
elements, species or compounds present in a sample.
● Structural analysis is the determination of the spatial arrangement of atoms in an element
or molecule or the identification of characteristic groups of atoms (functional groups).
● An element, species or compound that is the subject of analysis is known as an analyte.
● The remainder of the material or sample of which the analyte(s) form(s) a part is known
as the matrix.

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 Quality control in the process
Scope & Applications
1
industries Analytical data are required in a wide range of disciplines and situations
• of starting materials that include not just chemistry and most other sciences Important areas of
application include the following.
• of intermediates
• of products 2 Environmental analysis

• Monitoring and control of pollutants in

Clinical and biological
studies
• Measurement of nutrients, including trace
metals
• Measurement of naturally produced
chemicals (cholesterol, sugar, urea)
• Measurement of drug levels in body
Geological assays
• Measurement of metal concentrations in ores
and minerals
• Measurement of oil/gas concentrations in rocks
streams that are to be released to the
environment (in gas, liquid or solid form)
3
• Measurement of pollutants in the
environment (air/river/ground)
Fundamental and applied
4
research
• Chemical engineering: how much conversion
(or separation) do we obtain under these
conditions?
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• Organic molecule synthesis
2
 Classification of Analytical methods
The analytical methods are classified according to the depending upon the method of Analysis into:

Instrumental or
physicochemical
methods
These are concerned with the measurement of certain physical parameters
of a chemical system that are dependable on the nature of the system
components and vary in the process of reaction. These parameters include
electron potential, conductance, current, absorption and emission of
radiation…etc.
Examples: Spectroscopic techniques, Electrochemical techniques and
Separation Techniques
Classical or
Chemical methods
These depend on chemical reactions. In qualitative analysis,
identification methods involve reactions producing external
effects, e.g. formation of PPT or colored solutions, gas
evolution, etc. in quantitative analysis, chemical reactions
help in measuring the amount of reaction product or of the
reagent consumed.
Examples: Volumetric analysis and Gravimetric analysis 3
 Classification of Analytical methods

Instrumental or
Classical or
physicochemical
Chemical methods
methods
1- Procedure is simple, fast and accurate
1- procedure in some cases are complexed, tedious
2- cheap equipment and readily available in all labs
2- High expensive instruments, not available in all labs
3- No need for calibration curve
3- Calibration curve is essential
4- Suitable for mg samples
4- Suitable for samples at very low concentration

4
Basic Tools of Analytical
Chemistry
Fundamental SI Units of Importance to Analytical Chemistry

5
Common Prefixes

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 Chemical

Concentration is a general measurement unit stating the

amount of solute present in a known amount of solution
amount of solute
Concentration =
amount of solution
Concentration
There are many other expressions which can describe
concentration as in the next table

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Common Units for Reporting Concentration

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Basic Equipment

9
Basic Equipment

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 Analytical approach to
Identify and Define Problem Design Experimental Procedure
• What is the problem’s • Establish design criteria.
context? • Identify potential
• What type of interferents.
information is needed? • Establish validation criteria.
• Select analytical method.
• Establish sampling strategy.
Conduct Experiment & Analyze Experimental Data
Gather Data Calibrate
• Calibrate instruments • Reduce and transform data.
(Calibration) and • Complete statistical analysis.
equipment.
• Verify results.
• Standardize reagents.
• Interpret results.
• Gather data.
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 1 Accuracy, precision

Selecting an 2 Robustness, ruggedness

Analytical Method 3 Specificity, selectivity

The requirements of the
analysis determine the best
method. In choosing a method, 4 Availability of equipment
consideration is given to some
or all the following design 5 Amount of sample, analysis time, cost
criteria:
6 The background of the sample

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New Analytical method
Validation of analytical method involve the following criteria

Development

Optimization

Pre-validation

validation Re-validation

Application

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 Method validation
USP and ICH guidelines also add system suitability test for chromatography

Linearity and
Accuracy Precision Range

Limit of
Quantitation
Specificity/
Selectivity
Limit of Ruggedness/
Detection Robustness

Each parameter has specific acceptance criteria which different according to

assay type

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 Accuracy, precision and Robustness

Accuracy
Is the closeness of an experimental measurement or result to the true or accepted value.

precision
Refers to the reproducibility of analytical results. is the closeness of agreement between replicated
measurements or results obtained under the same prescribed conditions.

Robustness
When a method is relatively free from chemical interferences, we can use it on many analytes in a wide variety
of sample matrices. Such methods are considered robust.

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15
 Ruggedness, Specificity and Selectivity

Ruggedness
When a method is relatively insensitive to changes in experimental conditions such as temperature, acidity, or
reaction time etc. Such method are considered Rugged.

Specificity
An analytical method is specific if its signal depends only on the analyte

Selectivity
Refers to the ability of the method to discriminate a particular analyte in a complex mixture without
interference from other components.

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 ANALYTICAL TECHNIQUES AND METHODS

Analytical techniques
Chemical or physico-chemical processes that provide the basis for analytical measurements are described as
techniques.

Analytical methods
A method is a detailed set of instructions for a particular analysis using a specified technique.

Method validation
A process whereby an analytical method is checked for reliability in terms of accuracy, reproducibility and
robustness in relation to its intended applications.

Dr Adel Mohamed Ahmed 17

18
 Calibration and Standards

• Calibration or standardization procedure is required to establish the relation

between a measured physico-chemical response to an analyte and the amount or
concentration of the analyte producing the response.
• Used for instrumental methods
• Calibration is conducted by using of chemical standards
• Chemical standards A chemical standard is a material or substance of very high

Calibration purity and/or known composition that is used to standardize a reagent or calibrate an
instrument.

Materials or substances suitable for use as chemical standards are generally single compounds or elements. They must be of
known composition, and high purity and stability. Many are available commercially under the name AnalaR.

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 Calibration and

Are used principally in titrimetry to standardize a reagent (titrant) must be internationally

recognized and should fulfil the following requirements:
● be easy to obtain and preserve in a high state of purity and of known chemical
composition;
● be non-hygroscopic and stable in air allowing accurate weighing;
● have impurities not normally exceeding 0.02% by weight;
● be readily soluble in water or another suitable solvent;
Primary ● react rapidly with an analyte in solution;
● have a high relative molar mass to minimize weighing errors.

standards

Primary standards are used directly in titrimetric methods or to standardize solutions of secondary or working standards (i.e.
materials or substances that do not fulfill all of the above criteria, that are to be used subsequently as the titrant in a particular
method). Chemical standards are also used as reagents to effect reactions with analytes before completing the analysis by
techniques other than titrimetry.
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21
 Calibration and

Measure signal response vs. known analyte

concentration
The data is plotted and fit to a function to obtain
The equation of the “best” fit and the uncertainty in
the fit.
Typically the best fit is linear
y = mx+b
response = slope [c] + intercept
m is related to the method sensitivity

Calibration curve •Measure the sample response to determine the

concentration
Matrix effects must be minimal

A series of at least five calibration standards containing known amounts of the analyte and matrix components, if required. The
response of the detection system is recorded for each standard under specified and stable conditions and additionally for a
blank,(a standard prepared in an identical fashion to the other standards but omitting the analyte). The data is plotted as a
calibration graph.
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 Complete statistical analysis

Limit of detection (LOD): the lowest amount of an analyte that can

be detected at a known confidence level
Signal-to-noise: ratio of the average signal to the average level
of noise.
Limit of quantitation (LOQ): the range over which quantitative
measurements can be made (usually the linear range), often
defined by detector dynamic range
Linearity: the degree to which a response of an analytical

Calibration curve
detector to analyte concentration/mass approximates a linear
function
Dynamic range: range between the LOQ and limit of linearity

• All instrumental methods have a degree of noise associated with the measurement that limits the amount of analyte that can be
detected.
• Detection Limit is the lowest concentration level that can be determined to be statistically different from an analyte blank.
• Detection Limit is the concentration that gives a signal three times the standard deviation of the background signal. 23
Experimental Errors
Experimental
Errors • All measurement processes are subject to measurement
errors that affect numerical data and which arise from a
variety of sources.
• Data of unknown quality are useless!
• It is necessary to determine the magnitude of the accuracy
and reliability in your measurements. Then you can make
a judgment about their usefulness.

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 Experimental Errors

Absolute Error (E) - the difference between the experimental value and the true value.
Has a sign and experimental units:
E = x i− x t
Experimental value – true (acceptable) value

Relative Error (Er ): it gives an indication of how good a measurement is relative to

Absolute and Relative the size of the thing being measured.

It has a sign but no unite

Errors 𝑬𝒓 =
𝑿𝒊 − 𝑿𝒕
𝑿𝒕
× 𝟏𝟎𝟎%

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Types of Errors

Systematic Random Gross errors

Also called determinate errors, Also called indeterminate errors, Also called blunders
affect accuracy! affect precision!

Dr Adel Mohamed Ahmed 26

 Types of Errors

1. Instrument errors –
Failure to calibrate, degradation of parts in the instrument, power fluctuations, etc.

2. Method errors –
Errors due to no ideal physical or chemical behavior - completeness and speed of reaction,
interfering side reactions, sampling problems
1- Systematic or 3. Personal errors –

Determinate Errors
Occur where measurements require judgment, result from prejudice, color acuity
problems

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 Types of Errors

1. Potential instrument errors –

• Variation in temperature
• Contamination of the equipment
• Power fluctuations

1- Systematic or
• Component failure

All of these can be corrected by calibration or proper instrumentation maintenance.

Determinate Errors

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 Types of Errors

2- Method Errors
• Slow or incomplete reactions
• Unstable species
• Nonspecific reagents

1- Systematic or
• Side reactions

These can be corrected with proper method development.

Determinate Errors

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 Types of Errors

3- Personal Errors
a. Misreading of data
b. Improper calibration
c. Poor technique/sample preparation
d. Personal bias

1- Systematic or
e. Improper calculation of results

• These are blunders that can be minimized or eliminated with proper training and

Determinate Errors experience

• The Effect of Systematic Error - normally "biased“ and often very "reproducible".

Detection of Systematic Method Errors

1. Analysis of standard samples

2. Independent Analysis: Analysis using a "Reference Method" or "Reference Lab"

3. Blank determinations
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4. Variation in sample size: detects constant error only
 Types of Errors

• caused by uncontrollable variables which normally cannot be defined

• The accumulated effect causes replicate measurements to fluctuate randomly around
the mean.
• Random errors give rise to a normal or gaussian curve.
• Results can be evaluated using statistics
• Usually statistical analysis assumes a normal distribution
• The Nature of Random Errors – also called "indeterminate" and follow a predictable
pattern.

2-Random Errors • Error is the deviation from the "true value"

• Random error results in values that are higher or lower than the "true value".

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 Types of Errors

• Gross errors cause an experimental value to be discarded.

• Lead to outlier’s and require statistical techniques to be rejected.
• Examples of gross error are an obviously "overrun end point“ (titration), instrument
breakdown, loss of a crucial sample, and discovery that a "pure" reagent was actually
contaminated.
• We do NOT use data obtained when gross error has occurred during collection.

3-Gross Error

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Chemical Equilibrium
Dr. Adel Mohamed Ahmed
 Look &

Na2CO3 + CaCl2 2NaCl + CaCO3

In the lab, this reaction is completed, but in fact, it’s not.

The relative amounts of “reactants” and “products” determine the direction in which the reaction occurs, and
the final composition of the reaction mixture.
Na2CO3 + CaCl2 ↔ 2NaCl + CaCO3
When we mix together solutions of Na2CO3 and CaCl2, they react to produce NaCl and CaCO3. If we monitor
the mass of dissolved Ca2+ remaining and the mass of CaCO3 produced as a function of time, the result will
look something like the graph in Figure. At the start of the reaction the mass of dissolved Ca2+ decreases and
the mass of CaCO3 increases. Eventually, however, the reaction reaches a point after which no further changes
occur in the amounts of these species. Such a condition is called a state of equilibrium.
Dr Adel Mohamed Ahmed 33
 Equilibrium and
Na2CO3 + CaCl2 2NaCl + CaCO3

Equilibrium constant

Equilibrium
A system is at equilibrium when the
concentrations of reactants and products
remain constant.
For a reaction at equilibrium, the equilibrium constant determines the
relative concentrations of products and reactants, where the square-
bracketed terms are:
1. molar concentrations if they represent dissolved solutes.
2. partial pressures in atmospheres if they are gas-phase reactants or
products. 34
Types of Equilibrium Constants in Analytical Chemistry

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 Electrolyte and Non-electrolyte

• Some substances form ions, which are species possessing a charge. They
may attract molecules of solvent, may associate together, and may react
with other species to form complexes or a precipitate.
• Solvents with high dielectric constants (ɛr > 10), for example, water and
ammonia, are polar and are ionizing solvents, promoting the formation and
separation of ions in their solutions, whereas those where ɛr is about 2,
such as diethyl ether, tetrachloromethane and hexane are nonpolar and are
nonionizing solvents.

• Electrolytes : Are solutes which form ions when dissolved in water (or certain other solvents) and thus produce solutions that conduct electricity. They
may attract molecules of solvent, may associate together, and may react with other species to form complexes or a precipitate. Two types of electrolytes
are present:
• 1-Strong Electrolytes = solutes almost completely ionized
• 2.-Weak Electrolytes = solutes only partially Ionized
• Non electrolytes: Solution which not carry electrical charge and not ionized at all ex. Glucose in water
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Electrolyte and Non-electrolyte

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Applying the Ion-Product Constant for Water
Aqueous solutions contain small concentrations of hydronium and hydroxide ions as a result of the dissociation reaction
𝟐𝐇𝟐𝐎 ↔ 𝐇𝟑𝐎+ + 𝐎𝐇 −
An equilibrium constant for this reaction can be written as
𝐇𝟑𝐎+ 𝐎𝐇 −
𝑲=
𝐇𝟐𝐎 𝟐
The concentration of water in dilute aqueous solutions is enormous, however, when compared with the concentration of
hydronium and hydroxide ions. As a result, [H2O]2 can be taken as constant, and we write
𝑲𝒘 = 𝐇𝟑𝐎+ 𝐎𝐇 −
where the new constant Kw is given a special name, the ion-product constant for water.
If we take the negative logarithm of the last Equation, we discover a very useful relationship.
−𝒍𝒐𝒈𝑲𝒘 = −𝒍𝒐𝒈 𝐇𝟑𝐎+ − 𝒍𝒐𝒈 𝐎𝐇 −
By the definition of p-function,
𝒑𝑲𝒘 = 𝒑𝑯 + 𝒑𝑶𝑯
At 25°C, pKw = 14.00.

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Acids and Bases
 Acids and Bases
They defined as following:

1- Arrhenius Theory
Acids are substances which produce hydrogen ions H+ in solution & bases are substances which produce
hydroxide ions OH- in solution.
Limitations: 𝑯𝑪𝒍 + 𝑵𝑯𝟑 → 𝑵𝑯𝟒𝑪𝒍
2- Bronsted-Lowery Theory
Acids are proton donors & bases are proton acceptors
𝑯𝑪𝒍 ↔ 𝑯+ + 𝑪𝒍 − 𝑵𝑯𝟑 + 𝑯+ → 𝑵𝑯𝟒𝑪𝒍
Limitations: 𝑵𝑯𝟑 + 𝑩𝑭𝟑 ↔ 𝑵𝑯𝟑𝑩𝑭𝟑

3- Lewis Acids and Bases

Acids are Electron-pair acceptor & bases are Electron-pair donors

Dr Adel Mohamed Ahmed 39

 Examples of Lewis Acids and Bases

Generally, the Lewis definition of acids and bases is the most useful because it is the most inclusive of the three definitions. For
example, the Brønsted-Lowry definition of an acid includes HF but not BH3, which doesn't lose a proton when attached by the
lone pairs on a Lewis base.

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 Conjugate Acids and Bases

when an acid gives up a proton, the

product formed is a potential
proton acceptor and is called the
conjugate base of the parent acid.
Similarly, every base accepts a
proton to produce a conjugate acid.

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 Amphiprotic Species and Amphiprotic Solvents

Amphiprotic Species: Species that

have both acidic and basic properties
Amphiprotic solvents: that is, a solvent
that can
act either as an acid or as a base ,
depending on the
solute. Such as methanol, ethanol, and
anhydrous
acetic acid.

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 Autoprotolysis

Amphiprotic solvents undergo self-

ionization, or autoprotolysis, to form a
pair of ionic species.
The extent to which water undergoes
autoprotolysis at room temperature is
slight. Thus, the hydronium and
hydroxide ion concentrations in pure
water are only about 10-7 M.

Autoprotolysis (also called autoionization) is the spontaneous reaction of molecules of a substance to give a pair of ions.

Dr Adel Mohamed Ahmed 43

 Strengths of Acids and Bases
The strength of an acid (or base) is determined by the amount of IONIZATION.

Strong acids are completely

dissociated in water. Their conjugate
bases are quite weak.
Weak acids only dissociate partially in
water.
Their conjugate bases are weak bases.
The tendency of a solvent to accept or
donate protons determines the
strength of a solute acid or base
dissolved in it.

A differentiating solvent: solvent which will accept (or donate) a proton to one acid (or base) but not another (example: use of glacial acetic acid as solvent
to compare HClO4 and pyridine strength).
− − +
𝑪𝑯𝟑𝑪𝑶𝑶𝑯 + 𝑯𝑪𝑰𝑶𝟒 ↔ 𝑪𝑯𝟑𝑪𝑶𝑶𝑯𝟐+ + 𝑪𝑰𝑶𝟒 … … . . 𝑪𝑯𝟑𝑪𝑶𝑶𝑯 + 𝑪𝟓𝑯𝟓𝑵 ↔ 𝑪𝑯𝟑𝑪𝑶𝑶 +𝑪𝟓𝑯𝟓𝑵𝑯

A leveling solvent: That is one in which all acids or bases are dissociated to the same degree and have equal acid (or base) strengths.
− −
𝑯𝟐𝑶 + 𝑯𝑪𝑰𝑶𝟒 ↔ 𝑯𝟑𝑶+ + 𝑪𝑰𝑶𝟒 … … . . 𝑯𝟐𝑶 + 𝑯𝑪𝒍 ↔ 𝑯𝟑𝑶+ + 𝑪𝒍
Dr Adel Mohamed Ahmed 44
 pKa and pKb and pH

pKa = -log Ka
Ka is the equilibrium constant for the
dissociation of an acid
pKb = -log Kb
Kb is the equilibrium constant for the
dissociation of a base
pKw = pH+ pOH =14
pH = 14-pOH
pOH = 14-pH

pH is a measure of the hydrogen ion concentration, [H+]. It is calculated using the following formula: pH = -log [H+]
pOH is a measure of the hydroxide ion concentration, [OH-]. It is calculated using the following formula: pOH = -log [OH-]
Why measure pH?
Medical products, diagnosis, manufacture of soaps and shampoos, swimming pools, soil conditions for plants,….. Etc.
Dr Adel Mohamed Ahmed 45
 1 Litmus paper
Blue litmus paper (red = acid), Red litmus paper (blue = basic)

2 pH paper
(multi-colored)

3 pH meter

pH Testing
(7 is neutral, <7 acid, >7 base)

4 Universal indicator
(multi-colored)

5 Indicators
like phenolphthalein

6 Bleed-less pH paper

Dr Adel Mohamed Ahmed 46

 pH Meter

• It is an instrument tests the voltage

of the electrolyte, Converts the
voltage in electrolyte to pH
• Cost-efficient, Cheap, accurate in
results
• Must be calibrated with buffer
solutions

Dr Adel Mohamed Ahmed 47

 pH Scale

Pure water contains equal amounts

hydrogen ions and hydroxyl ions OH-,
at a concentration of 10-7 molar.
Therefore, the pH of neutral water
is -log (10-7) = 7.
Acids have pH values less than 7, down
to less than 1, while for alkalis, the pH
is greater than 7, up to 13 or more.

Dr Adel Mohamed Ahmed 48

 pH of strong acid and Strong Base

pH of strong acid pH of strong Base

pH = pCa pH = pKw - pCb
Find the pH of a 0.2 mol L-1 (0.2M) solution of HCl Find the pOH of a 0.1mol L-1 (0.1M) solution of
NaOH
1- Write the balanced equation for the dissociation of
the acid 1- Write the balanced equation for the dissociation of
+ −
the alkali
− +
𝑯𝑪𝒍 ↔ 𝑯 (𝒂𝒒) + 𝑪𝒍 (𝒂𝒒) 𝑵𝒂𝑶𝑯 ↔ 𝑶𝑯 (𝒂𝒒) + 𝑵𝒂 (𝒂𝒒)
0.2 mol L-1 HCl produces 0.2 mol L-1 H+ since HCl is 0.1 mol L-1 NaOH produces 0.1 mol L-1 OH- since
NaOH is a strong alkali that fully dissociates
a strong acid that fully dissociates
Use the equation to find the [OH-]:
Use the equation to find the [H+]:
pOH = -log [OH-]
pH=-log [H+] pOH = -log[0.1] = 1
pH = -log [0.2] = 0.7
pH = 14-1 =13

Dr Adel Mohamed Ahmed 49

pH of strong acid and Strong Base
Find the pH of a 0.2 mol L-1 (0.2M) solution of H2SO4
1- Write the balanced equation for the dissociation of the acid
+
𝑯𝟐𝑺𝑶𝟒 ↔ 𝟐𝑯 (𝒂𝒒) + 𝑺𝑶𝟒−𝟐 (𝒂𝒒)
0.2 mol L-1 H2SO4 produces 2 x 0.2 = 0.4 mol L-1 H+ since H2SO4 is a strong acid that fully dissociates
Use the equation to find the [H+]: pH = -log[H+] pH = -log[0.4] = 0.4

Find the pOH of a 0.1mol L-1 (0.1M) solution of Ba(OH)2

1- Write the balanced equation for the dissociation of the alkali:
−
𝑩𝒂(𝑶𝑯)𝟐 ↔ 𝟐𝑶𝑯 (𝒂𝒒) + 𝑩𝒂+𝟐 (𝒂𝒒)
Use the equation to find the [OH-]:
0.1mol L-1 Ba(OH)2 produces 2 x 0.1 = 0.2 mol L-1 OH- since Ba(OH)2 is a strong alkali that fully dissociates
Calculate pOH: pOH = -log[OH-]
pOH = -log[0.2] = 0.7

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pH of strong acid and Strong Base
What is the pH of a solution made by dissolving 2.5 g NaOH in 400 mL water
1- Determine number of moles of NaOH
𝑊𝑡(𝑔𝑚) 𝑁𝑎𝑂𝐻 2.5
x mol NaOH = = = 0.0625 mol NaOH
𝑀𝑤𝑡 (𝑁𝑎𝑂𝐻) 40

2-Calculate the molarity of the solution

NO.moles 0.0625
M= = = 0.15625 Molar
Volume (L) 0.4

3- Write the balanced equation for the dissociation of the alkali

− +
𝑵𝒂𝑶𝑯 (0.15625 molar) ↔ 𝑶𝑯 (0.15625 molar) + 𝑵𝒂 (0.15625 molar)
pOH = -log [OH-]
pOH = -log [0.15625] = 0.8
𝑝𝐻 = 14 – 𝑝𝑂𝐻 = 14 – 0.8 = 13.2
OR
kW = [H+] [OH-]
1 x 10-14 = [H+] [0.15625 M]
[H+] = 6.4 x 10-14 M
pH = -log [H+]
pH = -log [6.4 x 10-14 M] = 13.2 51
 pH of weak acid and Weak Base

pH of weak acid pH of weak Base

pH = 0.5 (pCa + pKa) pH = pKw - 0.5 (pCb + pKb)
Determine the pH of 0.30 M acetic acid (HC2H3O2) with the Ka of 1.8x10-5 Determine the pH of 0.15 M ammonia (NH4OH) with a Kb=1.8x10-5

1- Write an equilibrium equation for the acid: 1- Write the equilibrium equation for the base:
−
𝐻𝐶2𝐻3𝑂2 ↔ 𝐻 + + 𝐶2𝐻3𝑂2 NH4OH NH4+ + OH-
Start: 0.30 M 0M + 0M Start: 0.15 M 0M 0M
Equilibrium: 0.30 - x x x Equilibrium: 0.15 – x x x
2- Write the equilibrium expression and the Ka value: 2- Write the equilibrium expression and the Kb value:
Ka = [H+][C2H3O2-]/[HC2H3O2] = 1.8x10-5 Kb (1.8x10-5) = [NH4+][OH-]/[NH4OH]
Substitute the variables
Substitute the variables (disregard the "-x" because it is so small compared to 1.8x10-5 = (x)(x)/(0.15 - x) = x2/0.15
the 0.30) Ka (1.8x10-5) = (x)(x)/(0.30 - x) 1.8x10-5 = x2/0.30
x = [OH-] = 1.6x10-3 M
x = [H+] = 2.3x10-3
pOH = -log[OH-] = -log 1.6x10-3 = 2.80
pH = -log[H+] = -log 2.3x10-3 = 2.64 =======pH = 2.64
pH = 14.00 - 2.80 = 11.20

Dr Adel Mohamed Ahmed 52

 pH of Salts

Salts are ionic compounds formed in

the reaction between an acid and a
base.
- The reaction of an ion with water to
produce the conjugate acid and
hydroxide ion or the conjugate base
and hydrogen ion is called hydrolysis.

I-Neutral Salts (NaCl)

Na+ is derived from NaOH , a strong base and Cl- is derived from HCl, a strong acid
𝑁𝑎+ (𝑎𝑞) + 𝐶𝑙− (𝑎𝑞) →𝑁𝑎𝐶𝑙 (𝑠)
Na+ and Cl- ions do not react with water so the solution is neutral. Dr Adel Mohamed Ahmed 53
 pH of Salts

pH of Basic Salts pH of Acidic Salts

KCN NH4Cl
K+ is derived from KOH, a strong base and CN- is NH4+ is derived from NH3 , a weak base and Cl-
is derived from HCl, a strong acid
derived from HCN, a weak acid
+ − NH4 + (aq) + Cl − (aq) → NH4Cl (s)
𝐾 (𝑎𝑞) + 𝐶𝑁 (𝑎𝑞) → 𝐾𝐶𝑁 (𝑠)
Cl- ions do not react with water, but NH4+ ions do.
K+ ions do not react with water, but CN- ions do.
NH4 + + H2O → H3O + + NH3
− −
𝐶𝑁 + 𝐻2𝑂 → 𝐻𝐶𝑁 + 𝑂𝐻 hydrolysis hydrolysis
The OH- ions are produced, so the solution is basic. The H3O+ ions are produced, so the solution is
acidic

Dr Adel Mohamed Ahmed 54

 Common Ion Effect

The common ion effect is the

suppression of the ionization of a
weak acid or a weak base by the
presence of a common ion from a
strong electrolyte.

The solubility of an ionic precipitate decreases when a soluble compound containing one of the ions of the precipitate is added to
the solution. This behavior is called the common-ion effect.

Dr Adel Mohamed Ahmed 55

 • For many analytical measurements it is necessary to
control the pH so that it varies as little as possible.

Buffer Solutions • Solutions that resist changes in pH are known as buffer

solutions.
• They usually consist of a mixture of:
a weak-acid and its salt (conjugate base)
or a weak-base and its salt (conjugate acid)
• A buffer solution is a solution that resists change in pH
upon addition of small amounts of a strong acid or a
strong base.
• Buffers are used in all types of chemical applications
whenever it is important to maintain the pH of a solution
at a constant and predetermined level.
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 pH of Buffer solutions
Buffer solution may be acidic or basic, its pH determined by Henderson-Hasselbalch equations

Basic Buffer

Acidic Buffer
such as acetic acid/sodium acetate
such as ammonium chloride/ammonia

Dr Adel Mohamed Ahmed 57

Buffer Capacity
• Buffer Capacity is the amount of acid (or alkali) that, when added to 1 liter of buffer, will change its pH by 1 unit.
• There is a limit to the capacity of a buffer solution to neutralize added acid or base, and this limit is reached before all of one
of the buffer components has been consumed.
• In general, the more concentrated the buffer components in a solution, the more added acid or base the solution can
neutralize.
• As a rule, a buffer is most effective if the concentrations of the buffer acid and its conjugate base are equal.
Example1:
Calculate the pH of a buffer solution consisting of 0.1 M acetic acid and 0.1 M sodium acetate where the pKa = 4.76
Answer pH = pKa + Log (Salt/Acid)
pH = 4.76 + Log (0.1/0.1) = 4.76
Example2:
Calculate the pH of a buffer solution consisting of 0.7 M ammonia and 0.28 M ammonium chloride where the pKb = 4.76
pH = (pKw – pKb) + Log (Base/Salt)
pH = (14 – 4.76) + Log (0.7/0.28) = 8.64

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 Importance of buffer solution in pharmacy
1- Optimization of stability, solubility, and biological compatibility of the dissolved drugs in different liquid formulations like
syrups (pH 2-8), parental (pH 4-9) and eye drops.
2- Maintenance of the pH of human blood: The two buffers that are crucial to maintain the pH of human blood are:
1. Carbonic acid (H2CO3) & hydrogen carbonate (HCO31-)
2. Dihydrogen phosphate (H2PO41-) & monohydrogen phoshate (HPO42-)

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