PHARMACEUTICAL ANALYTICAL

CHEMISTRY

Dr. Ahmad Najjar

Dr. Ibrahim Khatib

1
CHAPTER 1

2
ANALYTICAL CHEMISTRY /
PHARMACEUTICAL ANALYSIS

Analytical chemistry is the study of the separation,

identification, and quantification of the chemical
components of natural and artificial materials.

Pharmaceutical analysis is the application of the

knowledge of analytical chemistry to analyze
pharmaceutical raw materials or finished products
where the principle of analytical chemistry is applied

3
Qualitative and Quantitative Analysis

4
ANALYTICAL CHEMISTRY

:Qualitative Analytical chemistry -1

- Focuses on the presence or absence of analyte
- Identification of analyte
- Recognized by color, boiling point, solubility, taste,… etc.

:Quantitative Analytical Chemistry -2

- Determination of concentration
- Gravimetric or titrimetric measurements, or instrumental
methods used are depending on physical properties
measurements like conductivity, electrode potential, light
emission absorption, mass to charge ratio, fluorescence, and
many more…

5
Quantitative Analytical methods

Quantitative Analytical methods are classified

:according to the final measurement step into

• Volumetric methods (volume)

• Gravimetric methods (weight)
• Instrumental methods (absorbance, optical rotation, etc…)

6
 QUANTITATIVE ANALYTICAL
METHODS
instrumental

7
ANALYTICAL APPROACH TO
SOLVING PROBLEMS

8
CHAPTER 5

9
Revision of basic
concepts

10
INTENDED LEARNING OUTCOMES
 Review of elementary concepts and mathematical
calculations

 Main laboratory techniques: weighing, volume

measurements, drying, solutions preparation,
decantation

11
SI measuring units

12
MOLAR MASS
It is the mass of one mole of substance, it is called:
Molar mass, M.wt. or f.wt. , its unit is (g/mol) or (mg/mmol)

Molar mass is calculated from the atomic masses of individual atoms

composing the molecule.

KMnO4?
NaOH?
CH3COOH?

13
14
MOLE 1 Mole of molecules ≡ avogadro’s num. of molecules
( avogadro’s num. = 6.02x1023 )

15
MOLE
also moles of substance = mass of substance / M.wt

36 g
e.g. 36 g of H2O contains  2 mol H 2 O
18 g/mol

16
17
Example
(a) How many glucose molecules are in 5.23 g of C6H12O6? (molar
mass is 180.0 g/mol)
(b) How many oxygen atoms are in this sample?
Answer
(a) Firstly, calculate the number of moles then calculate the
number of molecules from the number of moles
mass 5.23
moles    0.0291 mol
molar mass 180
number of molecules  number of moles  Avogadro' s no.
 0.0291 6.022x1023  1.75 1022

(b) Each molecule of glucose has 6 atoms of oxygen, therefore

number of oxygen atoms  6  number of glucose moelcules
 6  1.75  10 22  1.05  10 23

18
MOLE AND STOICHIOMETRY

19
MOLE AND STOICHIOMETRY
Stoichiometry is
the ratio between atoms in the molecular formula
and
the ratio between substances in the balance chemical equation

e.g. Glucose C6H12O6 the stoichiometric factors between C:H:O is 6:12:6

e.g. Ca(OH)2Ca2+ + 2OH- , the ratio between Ca(OH)2:Ca2+:OH- is 1:1:2

Q. If we have 5 moles of Ca(OH)2, how many moles of OH will produce?

Q. 3 moles of Fe2O3 contains ? mole of Fe atoms and ? mole of O atoms

20
 mass of A
Moles of A  (this is used generally if A is solid substance)
Molar mass of A

Molesof A  Molarconcentration of A  Volume of solution(thisis usedgenerallyif A is solutesubstancein a solution)

Pressure  Volume
Moles of A  (this is used generally if A is gaseous substance)
R(constant )  Temperatur e

Number of A particles
Moles of A  (this is used generally if number of A is known)
Avogadro' s Number (constant)

21
CONCENTRATION UNITS

Concentration is “The amount of a substance per defined space”

- We refer to the chemical species that we are looking for its concentration by
“Substance” or “Analyte” or “Solute”

Molarity (M) unit [used for solutions and it measure moles of solute per liters of solution]

Molarity = moles of substance / volume of solution (L)

M = mol / v

Q. Calculate the molarity of Cl-

in a solution made by dissolving 20 g of BaCl2 in
360 mL water? (M.wt of BaCl2 is 208 g/mol)

22
CONCENTRATION UNITS

Solution Preparation steps

23
(M.wt. AgNO3 is 169.9 g/mol)

(At.wt. K is 39.1 g/mol)

24
CONCENTRATION UNITS
For solutions also we can use the unit of g/mL or g/L or mg/L to express
the mass of solute per volume of solution
mass of solute (g)
concentration (g/L)  or M  M.wt
volume of solution (L)

(M.wt. Na2SO4 is 142 g/mol)

(M.wt. NaCl is 58.4 g/mol)

25
Concentration units
Part Per Million (ppm) and Part Per Billion (ppb) Units
These units could be used either if the solute was present in liquid,
solid or gas medium

ppm = [mass of substance (g) / mass of solution (g)] x 106

ppb = [mass of substance (g) / mass of solution (g)] x 109

- (Note that 1 ppm = 1000 ppb)

- we can convert molarity to ppm if we knew the density of the

solution.

- Density (D) is the mass (g) of one unit of the solution (generally mL
or L)

26
Concentration units

27
Concentration units
Percentage unit ( % )
Percentage unit is a concentration unit same as ppm and ppb, but
generally used for solid media. It could be expressed as
mass of solute (g)
- % w/w   100
mass of sample (g)
mass of solute (g)
- % w/v   100
volume of sample (mL)
volume of solute (mL)
- % v/v   100
volume of sample (mL)

Q. What is the percentage concentration (%w/w) of NaCl in a solution

made by dissolving 20.0 g NaCl in 200 mL water?

Q. Calculate the Na %w/w in the above solution? (M.wt. NaCl is 58.5

g/mol and At.wt. for Na is 23 g/mol)

Q. What is the molar concentration (M) of Glucose solution that has

%w/w of 15%? (M.wt. for glucose is 180 g/mol)

28
CONCENTRATION UNITS
Although molarity is widely used in chemistry, some chemists use a
unit of concentration in quantitative analysis called normality (N).
A one-normal solution contains one equivalent per liter. An
equivalent represents the mass of material providing Avogadro’s
number of reacting units. A reacting unit is a proton or an electron.
The number of equivalents is given by the number of moles
multiplied by the number of reacting units per molecule or
atom; the equivalent weight is the formula weight divided by the
number of reacting units (n).

No. of equivalents (eq)

Normality (N)   n  Molarity
Volume of solution (L)
mass (g)
No. of equivalents (eq)   n  moles
equivalent weight (g/eq)
Molecular weight (g/mol)
equivalent weight (g/eq) 
n (eq/mol)

29
CONCENTRATION UNITS
Reacting units (n), is depending on the chemical reaction. It may
vary most often in redox reactions, when different products are
obtained.
• For acids and bases, the number of reacting units is based on the
number of protons (i.e., hydrogen ions) an acid will furnish or a
base will react with.
• For oxidation–reduction reactions it is based on the number of
electrons an oxidizing or reducing agent will take on or supply.
• For most of ionic reactions it is based on the charge of the cation
or anion.

30
Concentration units
Example
Calculate the molarity of concentrated HCl solution that have a density of
1.188 g/mL and have % concentration of 36% w/w? (M.wt. HCl = 36.5 g/mol)

Answer
mole of HCl
Molarity of HCl concentrat ed 
volume of solution (L)
mass
1L of the solution has a mass of 1188 g , Density 
volume
 mass  Density  volume  mass  1.188g/mL  1000 mL  1188 g
36
this mass of solution has 36% of HCl, so mass of HCl  1188   427.68 g HCl
100
mass HCl 427.68 g
this mass of HCl contains no. of moles equal to   11.72 mol HCl
M.wt. HCl 36.5 g/mol
mol HCl 11.72
So 1L of the solution contains 11.72 mol HCl, then M HCl    11.72M
volume of solution (L) 1

1000  D  % w/w 1000 1.188 36

in another words, M HCl    11.72 M
M.wt. 36.5

31
Dilution
Dilution is a process in which we decrease the concentration of a
substance from high concentration (initial) to lower concentration
(final) by adding more solvent.

Number of moles is not changed, only the concentration and

volume are changed, therefore
Moles initial = Moles final
(Conc. x Vol) i = (Conc. x Vol) f

Example
What will be the volume of 0.2M NaCl solution that should be taken to
prepare 5L of 0.004M NaCl solution?
Answer
Initial: Conc. = 0.2M, Vol.=??
Final: Conc. = 0.004M, Vol.=5L
(M.V)i=(MV)f  0.2xVi = 0.004x5  Vi = (0.004x5)/0.2 = 0.1 L

32
Dilution
Dilution steps

33
Dilution

(M.wt. H2SO4 is 98.1 g/mol)

34
Dilution

35
Dilution

36
LABORATORY TOOLS
Volume measuring

Read from
meniscus at
eye level

37
LABORATORY TOOLS
Filtration

38
LABORATORY TOOLS
Temperature measurements

39
 LABORATORY TOOLS
Weighing

Analytical Top loading

balance balance

Triple beam
balance

Spatula
Weighing boats

40
HOW DO WE MAKE
?STOICHIOMETRIC CALCULATIONS
Chemical analysis is mainly employ the use of a balanced chemical
reaction.
In Volumetric or titrimetric analyses, the test substance Analyte (the
substance that we need to determine its concentration) reacts with
an added reagent of known concentration (standard solution). This
standard solution is typically delivered from a buret, therefore it is
called Titrant. Analyte concentration could be calculated from the
chemical relation between these two reactants.
In Gravimetric analyses, the Analyte is converted to a precipitated
Product according to a balanced chemical reaction. Analyte
concentration could be calculated from the chemical relation
between the analyte reactant and the precipitated product.

41
HOW DO WE MAKE
?STOICHIOMETRIC CALCULATIONS
Titration
The requirements of a titration are as follows:
1. The reaction must be stoichiometric. That is, there must be a well-
defined and known reaction between the analyte and the titrant.
2. The reaction should be rapid and quantitative. That is, the
equilibrium of the reaction should be far to the right so that a
sufficiently sharp change will occur at the end point to obtain the
desired accuracy.
3. There should be no side reactions; the reaction should be specific.
4. There should be a marked change in some property of the solution
when the reaction is complete. An indicator is generally added to
monitor this change.
5. The point at which an equivalent or stoichiometric amount of titrant
is added is called the equivalence point. The point at which the
reaction is observed to be complete is called the end point, that is,
when a change in some property of the solution is detected.

42
HOW DO WE MAKE
?STOICHIOMETRIC CALCULATIONS
Standard Solutions
A standard solution is prepared by dissolving an accurately weighed quantity of a
highly pure material called a primary standard and diluting to an accurately
known volume in a volumetric flask. Alternatively, if the material is not sufficiently
pure, a solution is prepared to give approximately the desired concentration, and
this is standardized by titrating a weighed quantity of a primary standard. A
solution standardized by titrating a primary standard is itself a secondary
standard.
A primary standard should fulfill these requirements:
1. It should be highly pure, with accurately known impurity.
2. It should be stable to drying temperatures, and indefinitely at room temperature.
3. It should be readily and relatively inexpensively available.
4. Although not essential, it should have a high formula weight.
5. If it is to be used in titration, it should possess the properties required for a
titration listed above. In particular, the equilibrium of the reaction should be far to

43
the right so that a sharp end point will be obtained.
HOW DO WE MAKE
?STOICHIOMETRIC CALCULATIONS
Classification of Titration Methods
1. Acid–Base. The end points of these titrations are easy to detect, either by
means of an indicator or by following the change in pH with a pH meter.
2. Precipitation. Titrant forms an insoluble product with the analyte. Again,
indicators can be used to detect the end point, or the potential of the
solution can be monitored electrically.
3. Complexometric. Titrant is a reagent that forms a water-soluble complex
with the analyte, a metal ion. The titrant is often a chelating agent like
Ethylenediaminetetraacetic acid (EDTA). Indicators can be used to form a
highly colored complex with the metal ion.
4. Reduction–Oxidation. These “redox” titrations involve the titration of an
oxidizing agent with a reducing agent, or vice versa. Appropriate indicators
for these titrations are available; various electrometric means to detect the
end point may also be used.

44
VOLUMETRIC CALCULATIONS

45
VOLUMETRIC CALCULATIONS

46
VOLUMETRIC CALCULATIONS

47
VOLUMETRIC CALCULATIONS

48
VOLUMETRIC CALCULATIONS

49
GRAVIMETRIC CALCULATIONS

50
CHAPTER 6

51
Review of Equilibrium

52
Review of Equilibrium

53
Equilibrium Constants for Dissociating or Combining
Species—Weak Electrolytes and Precipitates
When a substance dissolves in water, it will often partially or completely
dissociate or ionize. Electrolytes that tend to dissociate only partially are called
weak electrolytes, and those that tend to dissociate completely are strong
electrolytes.

Some species dissociate stepwise, and an equilibrium constant can be written for
each dissociation step. A compound A2B, for example, may dissociate as follows:

54
Equilibrium Constants for Dissociating or Combining
Species—Weak Electrolytes and Precipitates

When chemical species dissociate in a stepwise manner like this, the successive
equilibrium constants generally become progressively smaller. For a diprotic acid
(e.g., HOOCCOOH), the dissociation of the second proton is inhibited relative to
the first (K2 < K1), because the negative charge on the monoanion makes it
more difficult for the second proton to ionize.

If a reaction is written in the reverse, the same equilibria apply, but the
equilibrium constant is inverted. Thus, in the above example, for A + B  AB,
Keq(reverse)= [AB]/([A][B]) = 1/Keq(forward). If Keq for the forward reaction is 105, Kforward

= 1/Kbackward then Keq for the reverse reaction is 10−5.

55
Calculations Using Equilibrium Constants

** Repeat the calculations for K = 1x10-4 with and without approximation.

56
Calculations Using Equilibrium Constants
The Common Ion Effect

57
Calculations Using Equilibrium Constants
Equilibrium for complex systems
Mass balance equations

58
Calculations Using Equilibrium Constants
Equilibrium for complex systems
Charge balance equations

59
Calculations Using Equilibrium Constants
Equilibrium for complex systems
Systematic Approach

60
Calculations Using Equilibrium Constants
Equilibrium for complex systems
Systematic Approach

61
Calculations Using Equilibrium Constants
Equilibrium for complex systems
Systematic Approach

62
Activity and Activity Coefficients
The “effective concentration” of an ion is decreased by shielding it with other
“inert” ions, and it represents the activity of the ion. This “effective
concentration” of an ion in the presence of an electrolyte is called the activity
of the ion.

The activity of an ion ai is defined by: ai = Cifi , where Ci is the concentration of

the ion i and fi is its activity coefficient.

The activity coefficient varies with the total number of ions in the solution and
with their charge, and it is a correction for interionic attraction. In dilute
solution, less than 10−4M, the activity coefficient of a simple electrolyte is near
unity, and activity is approximately equal to the concentration. Activity
coefficient is a function of the total electrolyte concentration of the solution. The
ionic strength is a measure of total electrolyte concentration and is defined
by:

63
Activity and Activity Coefficients
Debye and Huckel derived a theoretical expression for calculating activity
coefficients, known as the Extended Debye–Huckel equation:

A and B are constants; the values are, respectively, 0.51 and 0.33 for water at
25°C. ai is the ion size parameter, which is the effective diameter of the
hydrated ion in angstrom units, Å.

64
Thermodynamic Equilibrium Constant
Equilibrium constants should more exactly be expressed in terms of activities
rather than concentrations

The numerical value of K°eq holds for all activities. Keq = K°eq at zero ionic
strength, but at appreciable ionic strengths, a value for Keq must be calculated
for each ionic strength.

65