TITRIMETRIC METHODS OF

ANALYSIS

1
 Introduction

Instrumental

Volumetric Separation
Wet
(Titrimetry) Spectro
Electroanly
Acid base
Precipitation
Gravimetry Complexometric
Redox
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 Titrimetry

Principle
An analyte is chemically reacted with a standard solution of
reagent of known concentration or with a concentration that
can be precisely determined. The amount (volume) of a
standard solution required to completely react with the entire
sample is used to estimate the purity or amount of the
sample.

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 Titrimetry…
Advantages
₰ Cheap to perform and do not require specialized apparatus
₰ Analysis can be automated
₰ They are absolute methods and are not dependent on the
calibration of the instrument or use of RS

Limitations
 Insensitive

 Time consuming if not automated

 Require large amount of sample and reagent

 Reaction of standard solutions with the analyte should be rapid and complete

4
 Titrimetry…
 Despite the difference in chemistry, all titrations share
several common features

A. Requirements for titration

 Stochiometric ratio should be known
 No complicating side reaction, rxn must be specific
 Concentration of the Titrant should be known
 Easy method of end-point detection

 The reaction should be rapid

 The reaction should be quantitative so that sharp change will occur
at the end-point

5
 Definition of some terms
 Volumetric titrimetry: consists of determination of volume of solution of
accurately known concentration required to react completely with the solution
of substance to be determined.
 Standard solution: the solution of accurately known concentration is called as
standard solution.
 Titrand/Analyte: the substance being titrated is called as titrand.
 Titrant: the solution of known concentration used in titration.
 Equivalence point or stochiometric endpoint: the theoretical point at which the
reaction between titrant & titrand is just complete.
 End point :the actual point at which reaction between titrant & titrand is just
complete.
 Indicator: it is an auxiliary substance which shows clear visual changes after
the reaction between titrand & titrant is practically complete.
 Titration error: in practice very small difference between theoretical endpoint
and actual endpoint usually occurs. This is called as titration error.
 Titrimetry…
Standard solution
 A standard solution is reagent used to titrate the analyte
 Should have known concentration
Two types-
 Primary and
 secondary standards
A primary standard is a highly purified compound (99.99%) material that
serves as reference.
 Requirements
 Must be easy to obtain, to purify, to dry and preserve in pure state
 It should be 100.00 % pure although 0.01 to 0.02 % impurities is tolerable if
accurately known.
 It should be stable at atmospheric conditions
 Should have high molecular weight
 It should be soluble in the conditions applied
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 Titrimetry…
 Low hygroscopicity (it is the ability of a substance to attract water molecules
from the surrounding environment through either absorption or adsorption)
and efflorescence (in chemistry, is the loss of water (or a solvent) of
crystallization from a hydrated or solvated salt to the atmosphere on exposure
to air).

Examples;
 Potassium hydrogen phthalate (usually called KHP) for standardization of
aqueous base and perchloric acid in acetic acid solutions.
 Sodium carbonate for standardization of aqueous acids: hydrochloric, sulfuric
acid and nitric acid solutions
 Potassium bromate (KBrO3) for standardization of sodium thiosulfate
solutions
 Titrimetry…
 Standards used as a standard that do not meet all these criteria are called
secondary standards

Exact concentration is determined by standardization

 Standardization : is the process of finding out the concentration of the

solution (20 standards) by using primary standard.

– In this process, standard solution is prepared by dissolving a fixed

weight of primary standard substance in solvent to prepare known
volume of solution.

Primary Secondary

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 Titrimetry…
Standard solutions are prepared
in two ways:

Direct method- Indirect method- a solution is

prepared to give approximately
a primary standard compound is the desired concentration, and
carefully weighed and dissolved this is standardized by titrating
against a weighed quantity of a
in exactly known volume of primary standard. Example;
solution. NaOH vs KHP

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 Titrimetry…
Equivalence Point and End point
Equivalence Point
is the point in titration where the number of moles of the titrant is
exactly the same as the number of moles of the titrand (Analyte) or
it is the point where the reaction between the titrant and the analyte is
completed.
Is a theoretical point that can not be determined experimentally and
• hence the completion of reaction is usually shown by a change of color
caused by a substance called an Indicator. This point is referred as End
Point.
• The difference between the end point volume and the equivalence point
volume is called Titration Error
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 Titrimetry…
Factors affecting end point detection
 Indicator selection
 Color change detection
 Quantity of indicators Generally, indicators are added in a very
small quantity approximately 0.0001-0.0004% of the solution being
titrated.
 Presence of colloidal substances: Colloidal particles are having
property to adsorb ions on their surface and this property leads to the
problems in detection of end point. Possibility of either premature or
delayed indicator color change and hence, the errors in detection of
end point.
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 Direct titration Vs Back titration
• Direct titration is a type of titration where the titrant is
allowed directly to react with the analyte.
 analysis of Cl- in raw materials using Ag+ as titrant

 Back titration is a type of titration where a measured

amount of a reagent is added to the analyte so that there is
a slight excess. After the reaction is allowed to go
completion, the amount of excess (un-reacted) reagent is
determined by titration with another standard solution.

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 When?
 the reaction is slow to go to completion

 the sample is volatile (e.g. NH3)

 the sample is insoluble (e.g. ZnO)

 the sample is thermolabile

 the end point of the back titration is clearer than

the end point of the direct titration

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 Examples

• Aspirin analysis
• Analysis of formaldehyde, H2CO.

– H2CO + I3 (excess) + 3OH- (aq) HCO-2 (aq)+ 3I-(aq) +

2H2O

– Unreacted I3- (aq) + 2 S2O32–(aq) S4O62- + 3I- (aq)

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 Back titration with Blank determination
 Blank titration is a titration with out the analyte.

 If the procedure involves heating and subsequent cooling of the sample

(e.g. to allow sample to dissolve), some of the volumetric reagents may be

lost either by evaporation or mechanically due to splashing or bubbling.

The indicator might also react with the reagent.

 Therefore blank titration is used to determine the exact amount of the

reagent, added in excess, which would react with analyte.

 The blank determination must be identical to the rest of the test determining

in every way except that there is no sample in the blank. This means that

heating times, dilution etc, must be duplicated exactly

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Titration Apparatuses; stopcock buret
 Titration Apparatuses; Pipetts

• A pipette (also called a pipet, pipettor or

chemical dropper) is a laboratory
instrument used to transport a measured
volume of liquid
Titration Apparatuses; Flasks

Erlenmeyer flask or conical flask.

 Volumetric flask

Volumetric flask — for preparing

liquids with volumes of high precision.
It is a flask with an approximately
pear-shaped body and a long neck with
a circumferential fill line.
 Calculations in titrimetry
Preparation of a solution from a pure solid chemical:
Vdesired X Ndesired X equivalent weight of solute = grams to be weighed or
Vdesired X Mdesired X molecular weight of solute = grams to be
weighed
Preparation of solution by dilution
Ncon x Vcon = Ndil. X Vdil. Or Mcon x Vcon = Mdil. X Vdil.
Standardization with a primary standard
VT x NT = grams (primary standard)/Equivalent weight
(primary standard)
VT x MT = grams (primary standard)/Molecular weight (primary
standard)
Standardization with another standard solution:
VT x NT = VST x NST or VT x MT = VST x MST

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 Calculations in titrimetry
Examples;
1. How would you prepare 500ml of a 0.15M solution of
NaOH from pure solid NaOH Pellets?
2. How many milliliters of KOH solution, prepared by
dissolving 60.0 g of KOH in 100 ml of solution, are
needed to prepare 450ml of a 0.7M solution? (Mol.wt
Of KOH is 56g/mole).
3. What is the molarity of HCl,36%w/w, and
having a density of 1.18g/ml?
4. How many grams of H2SO4( 17.45M,
density=1.82g/ml,95%w/w) are needed to
prepare 600ml of 0.1M solution?
 Titration curves
 Titration curve is plot of a variable related to a relevant
concentration as y-axis versus some measure of the amount of
titrant (e.g. volume) on the X-axis.

 A titration curve provides us with a visual picture of how a

property of the titration reaction changes as we add
the titrand to the titrant .

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Example

Figure-1: Acid-base titration curve

Titer value – gives the amount of analyte which reacts with 1 ml of the titrant.

Titer value = N or M × Eq. wt or M.wt

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 Steps in a titration

Most titrimetric analysis generally involve the following general steps:

1. Sampling

2. Titrant preparation

3. Standard preparation

4. Standardization of the titrant

5. Sample preparation (in a measurable form)

6. Doing the titration

7. Data analysis and interpretation.

Acid-Base Titration

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 Acid Base titration…

An acid-base titration is a simple experimental technique that

utilizes an acid-base reaction for quantitative purpose
Two types:



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 Common Titrant
For Bases For Acids
ф HCl NaOH
ф H2SO4 KOH
ф HClO4 HClO4

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 Acid-Base Titration…
 Detection of the end point: Indicators
Δ It is usually more convenient to add an indicator to the solution and
visually detect a color change.
Δ
An indicator for acid-base is a weak acid or weak base that is highly
colored.
Δ The color of the ionized form is markedly different from that of the non-
ionized form.
Δ One form may be colorless, but the other must be colored.
The substances are usually composed of highly conjugated organic
constituents that give rise to the color

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 Acid-Base Titration…
• Assume the indicator is weak acid, designated HIn, and assume
that the nonionized form is red while the ionized form is blue

HIn H++In-
(red) (Blue)

• One can write a Henderson-Hasselbalch equation for this,

just as other weak acids:
-
pH = pKa + log[In ]
[HIn]

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 Acid-Base Titration…
I. Direct titration of strong acid with strong base
 Characterized with large pH change around the equivalence
point. Eq pt. at pH = 7
 Before the equivalence point, pH depends on amount of
excess strong acid present
 After equivalence point, pH depends
on amount of excess base added.
 Indicator which changes color in
pH 4-10 is suitable (Methyl orange)
HCl vs NaOH

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 Titration curves for Direct titration of strong acid with strong base

For our first titration curve let’s consider the titration of 25.0
mL of 0.100 M HCl with 0.100 M NaOH. For the reaction of a
strong base with a strong acid the only equilibrium reaction of
importance is :
H3O+(aq) + OH–(aq) → 2H2O(l) …1
At the equivalence point we know from reaction 1 that
Moles HCl = moles NaOH
or
MaVa = MbVb
where the subscript ‘a’ indicates the acid, HCl, and the subscript ‘b’ indicates the base,
NaOH.

A) at 0.0 ml of NaOH added:

[H+]= 0.1 M
PH= - log [H+]
=- log (0.1)
=1.00
 Titration curves for Direct titration of strong acid with strong base

B) after adding 5 ml of NaOH is added:

Before the equivalence point, HCl is present in excess and the
pH is determined by the concentration of excess HCl.
[H+] = (0.025L )(0.1 mol/liter) – ( 0.005L)(0.1 mol/liter)
( 0.025 + 0.005)L
=0.002mol = 0.0067M
0.03 L
PH =-log ( 0.0667M)
= 1.18
 Titration curves for Direct titration of strong acid with strong base
C) after adding 10 ml of NaOH
[H+]=(0.025 L )(0.1 mol/liter) – (0.01L )(0.1mol/liter)
( 0.025 L + 0.01 L)
=0.0429M
PH= -log (0.0429M)
=1.37

D) after adding 20 ml of NaOH

[H+] = (0.025L)(0.1mol/liter) – (0.02L)(0.1mol/liter)
(0.025L + 0.02L)
=0.0111M
PH = -log(0.0111M)
=1.95
E) at the equivalence point (25mL of NaOH), pH =7
 Titration curves for Direct titration of strong acid with strong base

after the equivalence point- 35ml of NaOH added.

Finally, for volumes of NaOH greater than the equivalence point volume, the pH is
determined by the concentration of excess OH–.
[OH-]=( 0.035L)(0.1mol/liter) – (0.025L)(0.1 mol/liter)
(0 06L)
=0.0167M

POH= -log(0.o167M)
=1.78
,but PH+POH =14
PH=14-POH
=14-1.78
=12.22
G.after adding 50 ml of NaOH
[OH-]=(0.05L)(0.1 mol/liter) - (0.025L)(0.1mol/liter)
(0.075L)
= 1.48
PH= 14-1.48
=12.52
 Acid-Base Titration…
II. Direct titration of weak acid with strong base
 Equivalence point, PH > 7
 The transition range of the indicator for this titration of a weak acid must fall
within a pH range of 7 to 10.
 Most frequently used indicator in such titration is phenolphthalein.
 There is small pH change around
the equivalence point (Buffer)
 If indicator like Methyl red (4-6) is used,
there will be change in the color
before the equivalence point.
Salicylic acid, volatile acids HA vs NaOH

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 Acid-Base Titration…
III. Direct titration of strong base with strong acid
 The pH change in the region of the equivalence point are sufficiently
large
 Methyl orange is usually used as indicator (4-10).
 Before the equivalence point, pH depends on amount of excess strong

base present
 After equivalence point, pH depends on amount of excess acid added
 Sodium carbonate, Thiopentane injection

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 Acid-Base Titration…
IV. Direct titration of weak bases with standard strong acid

 The pH of the solution at the equivalence point, pH < 7

 Methyl red is the indicator used most frequently

 Before equivalence point, a buffer is formed and the pH does not

change very much with added acid

 After the equivalence point, pH depends on amount of excess acid

added

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Which one of the titration curves below corresponds to
the titration of a weak acid with strong base
 Acid-base titration cont…

Table-1: some important Acid/base indicators

Common Transition pKa color change Indicator type

name pH

Methyl orange 3.1-4.4 3.46 red-orange base type

Bromocresol green 3.8 -5.4 4.66 yellow-blue base type
Methyl red 4.2-6.3 5.00 red-yellow acid type
Phenol red 6.8-8.4 7.8 yellow-red acid type
Phenolphthalein 8.3-10 9.6 colorless-red acid type

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 Quantification by volumetric analysis
Direct Titration
Interpretation of the data obtained in volumetric
analysis is facilitated considerably by the use of
milliequivalent factor or titer value. TV (titer
value) is defined as the weight of a substance
chemically equivalent to one milliliter(1 ml) of a
standard solution( a titrant of known
concentration)
 Quantification by volumetric analysis
Example:
Ca(OH)2 + 2HCl→CaCl2 + 2H2O
1 mole of Ca(OH)2 = 2 mole of HCl
 74.09 g of ca(OH)2 = 2 mole of HCl
 74.09 g of Ca(OH)2 =1000ml of 2 molar HCl
X = 1 ml of 2 molar HCL
 X= 74.09 mg of Ca(OH)2
 Titer value of Ca(OH)2 is 74 .09 mg
A general formula which can be used for the calculation of the percentage
purity of a sample determined by direct titration is given by :

%C =( volume of titrant consumed )(titer value)  100

Sample weight or volume
 Quantification by volumetric analysis
Example : Assay of Sodium Bicarbonate

Method: 3 g of sodium Bicarbonate was weighed and mixed with 25 ml of water. The solution was
then titrated with 1M H2SO4 after adding methyl orange test solution to consume 17.7 ml .

Calculate its percentage strength.

Solution: 2(NaHCO3) + H2SO4→Na2SO4 + 2 H2O + 2 CO2

2moles of NaHCO3 = 1 mole of H2SO4

168.02 g of NaHCO3 = 1000ml of 1M H2SO4

X = 1 ml of 1M H2SO4

X= 168.02 mg=Titer value

%C= (TV) ( vol. of tit.) X 100

sample weight
= 168.02 X 17.7 X 100; = 99.13%
3000
 Quantification by volumetric analysis

Example: Assay of Furosemide 40 mg tablet

Method: A n equivalent of 0.25 g of the powdered tablet of Furosemide 40mg
,whose average weight is 140mg,is dissolved in 20 ml of dimethylformamide
and titrated with 0.1M NaOH using 2 ml of bromothymolblue solution.
a. Calculate the weight of the powder taken
b. Calculate its strength if each ml of 0.1M NaOH is equivalent to 33.07mg
of Furosemide and volume of titrant consumed is 7.6 ml.
c. Conclude up on its quality if its specification limits its strength to be
between (99 and 101) %.
d. Calculate the exact amount of active principle incorporated in one
tablet of the Furosemide based on the result obtained in part –b.
 Acid-base titration cont…
Application of Acid-base titration
 Water acidity (CO2, S, Fe(SO4)3, FeCl3)

 Water alkalinity (Hydroxides, carbonates and bicarbonates)

 Water hardness (Ca2+, Mg2+, Fe2+, Mn2+)
 Determination of free fatty acids in oils and fats
 Analysis of drugs

 Acidic drugs
 Basic drugs
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 Determination of some pharmaceutically important acids

a) Carboxylic acid derivatives;

Aceclofenac
Acexamic acid
(analgesic-anti-inflamatory)
Used for treatment of peptic ulcers

b) Carboxylic acid and phenolic derivatives

Aspirin, Antipyretic Levodopa, Used for treatment of
parkinson’s disease

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 Determination of some pharmaceutically important acids

c) Sulphonic acid derivatives:

Estropipatic acid
Etamsylate, Haemostatic agent

d) Arsenic acid derivatives;

Arsenillic acid, Antibacterial

Acetarsol 35
 Determination of some pharmaceutically important bases:
a) Primary amine compounds:

Amikacin, antibiotic

Sulphadiazine
36
 b) Secondary amine compounds:
Viloxazine, Antidepressant
Xylazine, Analgesic Piprazine hydrate

Tulobuterol, Beta-adrenoceptor agonist Pinadolol, Beta-adrenoceptor antagonist

37
C- Acid Salts of Basic Drugs

Amiloride hydrochloride

38
Non-aqueous titration

39
 Q
Methyl Dopa (BP)
– Weigh about 0.2g sample accurately and dissolve in a
mixture of 15ml of anhydrous formic acid, 30ml
anhydrous acetic acid and 30ml of 1, 4- dioxane. Titrate
with 0.1M Perchloric acid using crystal violet solution as
indicator
– State which type of volumetric assay is used for?

– Explain why titration of this type is sometimes required

and any precautions

40
 Con’t…
• Sometimes acid-base titrations are performed using a solvent
other than water.
•
There are several reasons why non-aqueous acid-base
titrations may be used instead of aqueous titrations
 If the sample is insoluble in water.
 If the Sample and/or titrant reacts with water in
undesirable ways.
 For the analysis of very weak acids or bases
41
 Cont’t…

 Substances which produce, upon reaction, products which cause a problem.

e.g. fatty acids which form soap during titration.

Fatty acids (water insoluble) + NaOH == RCOONa (soap) + H2O

The soap froth may cause a problem in aqueous media

 Selectivity is sometimes enhanced in non-aqueous solutions (analysis of analytes with similar

dissociation constants). In aqueous solutions, a difference of 2 pK units is necessary to observe
distinct endpoints. However, careful choice of solvent can sometimes allow the observation of
distinct endpoints that cannot be measured in aqueous solution

42
 Con’t…

• Some alkali metal salts of organic acids which form a heavy precipitates during
titrations e.g. sodium benzoate and sodium salicylate

43
 Relativity of acidity and basicity

An acidic substance can only function as an

acid in the presence of a base, and basic
substance can only act as a base in presence
of an acid.

44
Con’t…

45
 Con’t…
•
HCl gas function as acid only when dissolved in water, but not in dry
state (i.e. the ability of a substance to act as an acid or base will depend
very much upon the nature of solvent system which used.
• – H2O + HCl=====H3O+ + Cl-

– H2O + HCN=====H3O+ + CN-

– HCN + NH3=====CN- + NH4+
– HCN is very weak acid; it has a low tendency to transfer a proton to
water as a solvent
•The same acid might dissociate to a much greater degree in more basic solvents
This means that we can enhance the acidity by choosing a solvent more
basic (less acidic) than water. 46
 Con’t…

47
 Solvents for Non-aqueous titrations

• Protophilic solvents:
– They are basic solvents, more basic than water and have high ability
to accept protons. E.g. liquid ammonia, amines, ethers and ketones
HA + S == SH+ + A-
– They enhance the strength of weak acids (e.g. acetic and formic acid)
so that they have the same strength as strong acids (perchloric and
sulfuric acid). This effect known as the Leveling effect.

48
 Con’t…

– They are acidic solvents, more acidic than water and have the
affinity to donate protons. e.g. anhydrous hydrogen fluoride
and sulfuric acid.
HS + B === S- + BH+

– They enhance the strength of weak bases so that they have the
same strength as strong bases (Leveling effect).
49
 Con’t…
Aprotic solvents
– They are chemically inert, un-reactive under the conditions
used for determinations.
– E.g. CCl4 and benzene.
– They do not cause ionization of solutes and do not undergo
reactions with acids or bases.
– They are used only as vehicles or diluents.
– They have no leveling effect on acids or bases.
50
 Con’t…

– They are liquids that ionized to a slight extent and

exhibit both protogenic and protophilic properties.
– E.g. alcohols, water, acetic acid.

– They have both leveling and differentiating effects

51
– It is impossible experimentally to distinguish any difference
between the strength of two acid such as perchloric and
hydrochloric acids in aqueous media.

– Thus, water is said to exert leveling effect on HCIO4 and HCl since
both acids are much stronger acids than H3O+ (or because H2O is a
stronger base than either HCIO4 or HCl).

52
• It is the capability of a solvent to differentiate the strength of two acids

• Thus, acetic acid is said to exert differentiating effect on HClO4 and

HCl since CH3COOH2 + is a stronger acid than H3O + (or acetic acid is a
much weaker base than water).

• The reaction of HClO4 in acetic acid, however, shows a higher degree of

completion than the reaction of HCl with acetic acid.

53
 A. Titration of basic substances
Used for titration of:

– All amine types, alkaloides

– Sulphonamides and purines e.g. uric acid and its derivatives

– Halide salts of amines and quaternary ammonium salts.

– Alkali metal salts of organic acids.

54
 Con’t…
General Conditions:

– Solvent; glacial acetic acid is used mostly for dissolving sample &
standard.
– Titrant; Perchloric acid (0.1N), prepared by mixing 8.5 ml of 72 %
perchloric acid with 900 ml of glacial acetic acid and 30 ml of
acetic anhydride, then complete to 1 liter with glacial acetic acid.
– Indicator; 0.5% acetous crystal violet solution ( its color is changed
from blue to green)

55
Examples

56
 con’t…

• Aniline hydrochloride
(as halide salt of
amines): Mercuric
acetate is used to
replace the very weak
base (chloride) by
stronger base (acetate)

57
 Con’t…

Alkali metal salts of

organic acids such
as:phenobarbitone sodium
and sodium salicylate; they
serve as bases in glacial acetic
acid medium.

58
 B. Titration of acidic substances

– Very weak aromatic and aliphatic acids.

– Phenols and enols
– Imides and sulphonamides

• General conditions :
– Solvents; Benzene-methanol mixture, DMF (Dimethoxyformamide) and
ethylene diamine.
– Titrant; Potassium methoxide (0.1N), prepared by adding 4 gm of
potassium metal to a mixture of 40 ml methanol and 50 ml benzene then
complete to 1 liter with a mixture of both to give clear solution.
– Indicators; thymol blue or azo violet.

59
 Q
Methyl Dopa (BP)
– Weigh about 0.2g sample accurately and dissolve in a
mixture of 15ml of anhydrous formic acid, 30ml
anhydrous acetic acid and 30ml of 1, 4- dioxane. Titrate
with 0.1M Perchloric acid using crystal violet solution as
indicator
– State which type of volumetric assay is used for?
• Non aqueous acid base titration
– Explain why titration of this type is sometimes required
and any precautions
• Slide no.41-43
• Dry conditions should always maintained

60
Answer

61
 Review Questions
Q1. Explain in details the assay of
– Amantadine hydrocholoride

– Morphine hydrochloride

– Propranolol hydrochloride
Q2. How do you carry out the assay of the following drugs
(Use chemical equations)
 Metronidazole
 Adrenaline
 Salbutamol sulphate

63