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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5708_Библиотеки_им_академика_М_И_Перельмана.pdf
37
Volumetric Analysis
titration. The difference between the titrations represents the amount of alkali
required by the indomethacin.
or
Pipette out 10 mL of indomethacin solution in a conical flask. Add 23 drops
of phenolphthalein indicator in it and titrate it with previously standardized
sodium hydroxide solution until a permanent pink colour is obtained.
Reaction involved
Indomethacin
1-(4-chlorobenzoyl)-5-methoxy-
2-methyl-1H-indole-3-acetic acid
NaOH
Sodium hydroxide
H
2
O
Water
N
CH
3
O
CH
2
COOH
MeO
Cl
Sodium salt of indomethacin
sodium-1-(4-Chlorobenzoyl)-5-methoxy-
2-methyl-1H-indole-3-acetate
N
CH
3
O
CH
2
COONa
MeO
Cl
THEORY Indomethacin, a nonsteroidal anti-inflammatory indole derivative
(NSAID). It contains free carboxylic group which reacts with alkali to give
sodium salt of indomethacin.
Equivalent factor
1 NaOH { 1 C
19
H
16
O
4
NCl
1000 mL of 1 N NaOH { {(19 u 12) (16 u 1) (4 u 16) (1 u 14)
(1 u35.5)} g of indomethacin
1000 mL of 1 N NaOH { (228 16 64 14 35.5) g of indomethacin
1000 mL of 1 N NaOH { 357.5 g of indomethacin
1 mL of 1 N NaOH { (357.5/1000) g of indomethacin 0.3575 g of
indomethacin
Calculation
1 mL of 1 N NaOH { 0.3575 g of indomethacin
a mL of 1 N NaOH { (0.3575 u a) g of indomethacin
a mL of yN NaOH { (0.3575 u a u y) g of indomethacin
Since 10 mL of Indomethacin solution contains (0.3575 u a u y) g of indomethacin
1 mL will contain {(0.3575 u a u y)/10} g of indomethacin
100 mL will contain {(0.3575 u a u y u 100)/10} g of indomethacin
38
Practical Pharmaceutical Analytical Chemistry
So
g mL of Indomethacin
Equivalent factor Burette reading
Norm
/100
u
u
aality NaOH
()
u 100
10
Pharmaceutical use
1. It is used as an analgesic.
2. It is used as an anti-inflammatory agent.
3. It is used as an antipyretic.
Category: NSAID
Result The given indomethacin solution was found to contain ……
g/100 mL of indomethacin.
Experiment 15 To find out g/100 mL of sodium benzoate in the given
sample.
IP followed: 1996
Principle: Acidimetric determination
Molecular formula: C
7
H
5
O
2
Na
COONa
Molecular weight: 144
Indicator: Bromophenol blue ()
IP limit: The sample contains not less than 99.0% and not more than 100.5%
of sodium benzoate, calculated with reference to the dried substance.
Procedure
Weigh 1.5 g of sodium benzoate and dissolve it in 25 mL of water. Further, add
75 mL of ether and 2
–3 drops of bromophenol blue indicator. Titrate it with
0.5 N hydrochloric acid while mixing the water and ether layers well by shaking
until a light green colour persists in the water layer.
or
Pipette out 10 mL of sodium benzoate solution in a conical flask. Add 10 mL of
ether and 23 drops of bromophenol blue indicator. Titrate it with previously
39
Volumetric Analysis
standardized hydrochloric acid while mixing the water and ether layers well by
shaking until a light green colour persists in the water layer.
Reaction involved
Sodium benzoate
HCl
Hydrochloric acid
NaCl
Sodium chlorideBenzoic acid
COONa
COOH
THEORY Sodium benzoate is the sodium salt of benzoic acid. It reacts with
hydrochloric acid to give benzoic acid and sodium chloride which is a salt. Ether
is added to dissolve formed benzoic acid as it is insoluble in water.
Equivalent factor
1HCl { 1C
7
H
5
O
2
Na
1000 mL of 1 N HCl { {(7 u 12) (5 u 1) (2 u 16) (1 u 23)} g of sodium
benzoate
1000 mL of 1 N HCl { (84 5 32 23) g of sodium benzoate
1000 mL of 1 N HCl { 144 g of sodium benzoate
1 mL of 1 N HCl { (144/1000) g of sodium benzoate 0.144 g of sodium
benzoate
Calculation
1 mL of 1 N HCl { 0.144 g of sodium benzoate
a mL of 1 N HCl { (0.144 u a) g of sodium benzoate
a mL of yN HCl { (0.144 u a u y) g of sodium benzoate
Since 10 mL of sodium benzoate solution contains (0.144 u a u y) g of sodium
benzoate
1 mL will contain {(0.144 u a u y)/10} g of sodium benzoate
100 mL will contain {(0.144 u a u y u 100)/10} g of sodium benzoate
So
g /100mL of sodium benzoate
Equivalent factor Burette reading
No
×
×
rrmality HCl
()
×100
10
40
Practical Pharmaceutical Analytical Chemistry
Pharmaceutical use
It is used as a preservative in carbonated and still beverages, syrups, etc.
Category: Antifungal preservative
Result The given sodium benzoate solution was found to contain ……
g/100 mL of sodium benzoate.
2.2 Oxidation–Reduction (Redox) Titrations
The reactions which involve a change in the oxidation states of reactants
are called as oxidation–reduction reactions. In simpler terms, oxidation is
known as the addition of oxygen or removal of hydrogen and reduction is
known as addition of hydrogen and removal of oxygen. According to the
electronic concept, oxidation–reduction is the reaction in which electrons
are transferred from one reactant to the another. Oxidation is defined as
the loss of electron and reduction is defined as gain of electron, i.e. they
must occur simultaneously. When a substance gives an electron there must
be another substance to receive it. The oxidation–reduction reactions involve
the transfer of electrons from one substance to other and these two processes
occur simultaneously.
If one substance is oxidized then the other must be reduced. The substance
which loses the electron(s) and gets itself oxidized is called as a reducing agent
and the substance which gains electron(s) and gets itself reduced is called an
oxidizing agent. A reaction involving oxidation–reductionis also termed as redox
reaction.
AB
1
Reducing agent
or
Reductant
3
Oxidizing agent
or
Oxidant
++
+⎯→⎯⎯ AAB
A - e A loss of electron; reductant
B+e B
22
12
32
++
++
++
+
⎯→⎯⎯
()
⎯→⎯⎯ ggain of electron; oxidant
()
Commonly used oxidizing agents are potassium permanganate, potassium
dichromate, potassium iodate, potassium bromate, ferric sulphate, lead dioxide,
iodine, and potassium periodate.
Commonly used reducing agents are antimony trioxide, ferrous sulphate,
sodium thiosulphate, stannous chloride, oxalic acid, titanous sulphate and sodium
arsenite.
Commonly used primary standards are potassium iodate, potassium bromate,
potassium dichromate, arsenous oxide and sodium oxalate.
41
Volumetric Analysis
2.2.1 Determination of Equivalent Weight
Three methods that can be used to determine the equivalent weight include:
1. Available oxygen method
2. Ion electron method
3. Oxidation number method
Available Oxygen Method
The equivalent weight of an oxidant or reductant is defined as its parts by weight
which reacts with or produces at parts by weight of available oxygen.
Example
1. Potassium permanganate
The reduction of potassium permanganate in acidic medium can be represented
by the following equation:
23 235
424 24 42
KMnO H SO K SO MnSO H O O+⎯→⎯⎯⎯ + + +
[]
Here 2KMnO
4
{ 5[O]
or 2 u molecular weight { 5 u 16
or molecular weight/5 16/2
or molecular weight/5 8
Equivalent weight of potassium permanganate in acidic medium is 1/5th of the
molecular weight.
So, the equivalent weight of potassium permanganate 156/5 31.6
2. Potassium dichromate
K Cr O H SO K SO Cr SO H O O
227 24 24 2 4
3
2
443+⎯→⎯⎯⎯ +
()
++
[]
Here K
2
Cr
2
O
7
{ 3[O]
or molecular weight { 3 u 16
or molecular weight/3 16 2 u8
or molecular weight/6 8
Equivalent weight of potassium dichromate in acidic medium is 1/6th of the
molecular weight.
So, the equivalent weight of potassium dichromate 294.18/6 49.03
3. Oxalic acid
|[]
COOH
COOH
HO O CO HO⋅+⎯→⎯⎯⎯ +223
222
42
Practical Pharmaceutical Analytical Chemistry
Here, (COOH)
2
{ [O]
or molecular weight {16
or molecular weight 2 u 8
or molecular weight/2 8
Equivalent weight of oxalic acid is 1/2 of the molecular weight.
So, equivalent weight of oxalic acid 126/2 63
Ion Electron Method
In all oxidationreduction reactions, the total number of electron gained by
the oxidizing agent must be equal to the total number of electron lost by the
reducing agent. This principle is followed in valency redox reaction and hence
this method is called as ion electron method. The gram equivalent of a reactant
containing element which is oxidized or reduced can be calculated on the basis
of the number of electron transferred to or from one atom of an element. If
we do change in the number of electron or ion in any oxidationreduction
reaction then the equivalent weight is calculated. The equivalent of an oxidant
and reductant is the mole number of electron which one mole of substance gains
or losses in reaction under consideration.
Example
1. Potassium dichromate
Cr O H e Cr H O
2 7
3
2
14 6 2 7
++− +
++⎯→⎯⎯⎯ +
Here, gain of electron is 6, which leads to conversion of Cr
2
O
7
2
to Cr
3
. Hence,
equivalent weight will be 1/6th of the molecular weight.
So, the equivalent weight of potassium dichromate 294.18/6 49.03
2. Oxalic acid
HCO CO e
224 24
2
2⎯→⎯⎯⎯ +
−−
Here the loss of electron is 2. So, the equivalent weight of oxalic acid is 1/2
of molecular weight.
So, equivalent weight of oxalic acid 126/2 63
Oxidation Number Method
Oxidation number of an element is the number which may be applied to that
element in a particular compound that indicates the amount of oxidation or
reduction which is required to convert one atom of an element from free state
to that in the compound. If oxidation is necessary to effect the change then the
oxidation number is positive but if reduction is necessary to affect the change
then the oxidation number is negative.
43
Volumetric Analysis
Following are the rules that are applied to determine the oxidation number:
1. Oxidation number of all free elements is zero.
2. Oxidation number of a compound is always zero.
3. Oxidation number of the hydrogen atom in its compound is 1, except in
certain hydrides.
4. Oxidation number of O is 2 and O
2
is zero.
5. Oxidation number of sodium and potassium in their compounds is 1.
Example
1. Potassium permanganate
KMnO MnSO
4
18
7
4
2
2
+−
+
+
−
⎯→⎯⎯⎯
Since the oxidation number of a compound is always zero
Therefore, KMnO
4
0
or (1) (X) (2 u 4) 0
where X is the oxidation number of Mn in KMnO
4
or 1 X (8) 0
or 1 X 8 0
or X 7 0
or X 7
Similarly, for MnSO
4
MnSO
4
0
or (X) (2) 0
where X is the oxidation number of Mn in MnSO
4
or X 2 0
or X 2
Change in oxidation number 7 2 5
So, the equivalent weight of potassium permanganate in acidic medium is
1/5th of molecular weight.
The equivalent weight of potassium permanganate 156/5 31.6
2.
Potassium dichromate
KCrO Cr SO
227
12 14
12
24
3
6
6
−+
+
+
−
⎯→⎯⎯⎯
()
Since the oxidation number of a compound is always zero
Therefore, K
2
Cr
2
O
7
0
or (1 u 2) (X) (2 u7) 0
where X is the oxidation number of Cr in K
2
Cr
2
O
7
or 2 X (14) 0
or 2 X 14 0
44
Practical Pharmaceutical Analytical Chemistry
or X 12 0
or X 12
Similarly, for Cr
2
(SO
4
)
3
Cr
2
(SO
4
)
3
0
or (X) (2 u 3) 0
where X is the oxidation number of Cr in Cr
2
(SO
4
)
3
or X 6 0
or X 6
Change in oxidation number 12 6 6
So, the equivalent weight of potassium dichromate is 1/6th of molecular
weight.
The equivalent weight of potassium permanganate 294.18/6 49.03
3. Oxalic acid
HCO CO HO
224
28
6
2
4
4
2
23
+−
+
+
−
⎯→⎯⎯⎯ +
Since, oxidation number of a compound is always zero
Therefore, H
2
C
2
O
4
0
or (1 u 2) (X) (2 u 4) 0
where X is the oxidation number of C in H
2
C
2
O
4
or 2 X (8) 0
or 2 X 8 0
or X 6 0
or X 6
Similarly, for CO
2
CO
2
0
or (X) (2 u 2) 0
where X is the oxidation number of C in CO
2
or X 4 0
or X 4
Change in oxidation number 6 4 2
So, the equivalent weight of oxalic acid is 1/2 of molecular weight.
The equivalent weight of oxalic acid 126/2 63
2.2.2 Iodimetric and Iodometric Titration
Oxidation and reduction involving iodine are very useful in titrimetric analysis
because iodine can be conveniently and accurately titrated with standard
thiosulphate solutions.
Titrimetric methods involving iodine are of two types:
1. Iodimetric titration
2. Iodometric titration
45
Volumetric Analysis
Iodimetric Titration
Determinations which involve direct titration with iodine are called as iodimetric
titration. The number of such reactions is limited because iodine is a weak oxidizing
agent and today most of these can be done by some other methods rather than by the
use of iodine. Iodine oxidizes the thiosulphate ions quantitatively to tetrathionate
ions. Some of the determinations which is well obtained by this method are:
s Assay of ascorbic acid
s Determination of antimony sodium tartarate and antimony potassium
tartarate
s Determination of dimercaprol
s Determination of carbazone tablets
s Determination of hydrogen sulphide
Iodometric Titration
Iodometric titration deals with the titration of iodine liberated in the chemical
reaction. In iodometric methods, compound which is to be analyzed is generally
treated with an excess of potassium iodide (because sodium iodide is less reactive
than potassium iodide). Iodine is liberated quantitatively and is then titrated
quantitatively with standard solution of sodium thiosulphate or arsenous acid.
These methods can be used for the analysis of almost any strong oxidizing
agent. Consequently, there are many more applications of iodometric methods
as compared to iodimetric methods. Some of the determinations which is well
obtained by iodometric method are:
s Standardization of potassium chromate with sodium thiosulphate
s Assay of copper sulphate
s Assay of ferrous sulphate
s Assay of bromates like potassium bromide and sodium bromide
s Assay of iodates like potassium iodate and sodium iodate
s Assay of chlorates
s Assay of nitrous acid
s Assay of lugol’s solution
s Assay of cerric sulphate
s Assay of periodate
2.2.3 Redox Indicators
An oxidationreduction indicator is a compound which exhibits different
colour in oxidized and reduced form. Oxidationreduction indicators should
mark the sudden change in the oxidation potential in the neighborhood of the
equivalent point in oxidationreduction titration. The ideal oxidationreduction
indicators will be the one with an oxidation potential intermediated between
that of the solution titrated and that of the titrant and which exhibit a sharp,
readily detectable colour change.
46
Practical Pharmaceutical Analytical Chemistry
There are three types of visual redox indicators:
1. Self indicator
2. External indicator
3. Internal indicator
Apart from these indicators, end point can also be detected by potentiometric
titration.
Self Indicator
Titrant can itself act as an indicator, i.e. after the completion of titration it gives a
colour which indicates the end point. Example: Potassium permanganate.
Drawback: A slight excess of the titrant is always present at the equivalence point.
Remedy: For accurate result, blank titration should be done.
External Indicator
In this titration, indicator is not added to the solution but the titration liquid is
taken out from time to time and added to the indicator solution kept aside.
Example: Potassium ferricyanide solution, potassium hexacyanoferrate solution,
starch paper and potassium ferrocyanide solution.
Drawback: Excess titrant present immediately after the end points gives a visible
reaction with specific reagent.
Internal Indicator
They are much similar to the acidbase indicator. The external indicator gives
one colour in an oxidizing medium and a different colour when it is added to a
solution of reductant. Example: Diphenylamine, starch solution, etc.
Serial no. Indicator Reduced form Oxidized form
1 Nitroferroin (5-nitro-1,
10-phenanthroline iron sulphate)
Red Pale blue
2 1,10-Phenanthroline iron sulphate Red Pale blue
3 5,6-Dimethyl ferroin Red Pale blue
4 4,7-Dimethyl ferroin Red Pale blue
5 N-Phenyl anthranilic acid Colourless Purple red
6 Diphenylamine sulphonic acid Colourless Red violet
7 Diphenyl benzidine Colourless Violet
8 Diphenyl amine Colourless Violet
9 Methylene blue Colourless Blue