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2- COMPLEXOMETRIC
TITRATIONS

⚫ When a metal ion combines with a molecule which can

donate electrons,
– the resulting compound is termed as a complex and the
process complexation.
⚫ Metal is the central ion while the non-metal, which gives
pairs of electrons is said to be Legand.
– Therefore, if a given legand gives one pair of electrons it is
said to be
⚫ monodentate,

⚫ two pairs-bidentate,

⚫ more than two pairs-multidentate.

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⚫ Titrant
⚫ The most commonly used titrant is ethylenediammine tetraacetic
acid, EDTA.
NaOOC.H2C CH2COOH
N CH2.CH2 N
HOOC.H2C CH2COONa

•It is a hexadentate ligand (6-sites of donation) that is 4-carboxilic

acids (4 pairs of electrons),2-ammines(2-pairs of electrons). It can
be represented as H4Y (tetraprotic).
•H4Y + H2O → H3Y + H3O+ ;PH ≤ 3
•H3Y + H2O →H2Y2- + H30+ ;PH(3-6)
•H2Y2- + H2O →HY3- + H30+ ;PH (6-9)
•HY3- + H20 →Y4- + H30+ ; PH> 10
•This implies that Y4- is the most effective complexing agent with
metals. Therefore PH must be adjusted to be greater than 10 , by
using a buffer solution, for complete complexation of metals.

⚫ Indicators:
– are organic compounds which form colored complex ions with the
metal ion in high Dilution.
– The complexed and uncomplexed forms have of the indicator
have different colors.
– Common indicators in complexometric titrations

Name of the Color of the free In Color of the metal

indicator complex
Erichrome Orange Wine red
Xylenon orange Yellow Red
Murexide Violet Yellow
•AlIn + EDTA → Al EDTA + In-
(Wine red) (Orange)

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Some Important Applications of Complexometric reactions:

(1) Determination of Water Hardness by
EDTA titrations:

1- Titration using eriochrome black-T

indicator and ammonia buffer at pH 10,
gives total hardness (Ca2+ + Mg2+).

2-Titration using murexide indicator and (2N)

NaOH at pH 12, gives calcium hardness
only.
Magnesium hardness = total - calcium
hardness.

(2) Determination of Pharmaceutical compounds having Chelating

properties: Examples:

Carbidopa
Apomorphine

8-Hydroxyquinolines

Adrenaline

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(2) Determination of Pharmaceutical compounds which

containing metal ions that undergo complexation
reactions
⚫ Examples:
– Aluminum, Calcium, magnesium and zinc salts of pharmaceutical
importance:
⚫ (A) Inorganic salts:
– Aluminum potassium sulfate, Aluminum chloride
hexa-hydrate, dried Aluminum hydroxide, Aluminum
acetate, dried Aluminum phosphate & Aluminum
magnesium silicate.
– Calcium sulfate, Calcium carbonate & Calcium
Oxide
– Barium sulfate
– Magnesium sulfate, Magnesium oxide & Magnesium
carbonate
– Zinc sulfate and Zinc Oxide
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(B) Organic Salts :

Zinc undecenoate
Aluminium Glycinate

Zinc acexamate
Calcium folinate

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Calcium levulinate dihydrate

Calcium gluconate

Calcium pantothenate

Calcium ascorbate

Calcium dobesilate

⚫ Dissolve 120 mg of MgSO4 (Epsom salt) in 100ml of

water , add 5ml of PH-10.9 buffer solution ,5 mg of
mordant black indicator and titrate the solution with
0.05M EDTA .
– Calculate the percentage strength of the Epsom salt if its
titer value is 6 mg and the color of the indicator is changed
after exactly 18.8 ml of the titrant is consumed.
Solution:
%C = TV X Volume of titrant consumed x 100
Sample taken
=6 x 18.8 x 100
= 94%

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Example: Determination of Aluminium

⚫ Dissolve about 13.6mg of aluminum in dilute HCl ,add strong
ammonia (10ml),50ml of 0.05 M EDTA ,add 2ml of dithiozone
test solution as an indicator and titrate the excess of EDTA with
0.05M ZnSO4 untill the color of the solution changes from
green-violet to rose-pink.
– Calculate the percentage strength of aluminum if the excess amount of
EDTA required 40 ml and the equivalent weight of aluminum is 26.98g.
Solution:
%C = (LTNT-LBTNBT)EWsol. x 100
Sample taken
=((0.05x0.05) – (0.04 x 0.05)) x 26.98 x 100
13.6
=99.19%

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(3) Precipitimetric Titrations

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⚫ As the name indicates, this is a titration where formation

of insoluble solids is observed around the end point of
the titration.
⚫ End point detection:
– Amperometric
– Chemical method(indicator)
– Potentiometry
⚫ Precipitimetric Titrations (Main types): including
– Argentometric titrations
– Mercurimetric titrations
– Other types

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⚫ Argentometric titration is a kind of precipitation titration

which uses silver nitrate of known concentration for
quantification of substances.
– It is broadly classified in to two parts:
Mohrs method:
is a direct titration method where AgNO3 of known concentration
as a titrant and potassium chromate as indicator.
Example:
⚫ NaCl + AgNO3 → AgCl (ppt) +NaNO3
– Slight excess of the titrant reacts with the indicator to give a
color to detect end point. Once chloride ion is consumed silver
ion reacts with chromate to form Ag2Cro4, which has a reddish
brown color.

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⚫ Chloride is more reactive towards silver ion than

chromate.
– The titration must be carried out at a neutral or slightly alkaline
media because
– in acidic medium (PH less than 6) chromic acid from chromate
can be formed,
– when PH> 10 AgOH can be formed which causes end point
detection problem.
Example:
⚫ Determination of NaCl iv preparation (0,9%). Take volume of the
0.9% NaCl iv infusion equivalent to 0.09 g of NaCl and titrate with
0.1N AgNO3 using K2CrO4 indicator.
– Calculate the volume that must be pipated out.
– Calculate the percentage strength of the drug if each ml of the titrant is
equivalent to 5.58mg and volume of titrant consumed is 15.3 ml

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Other applications:
⚫ KI
⚫ Sodium nitroprusside
⚫ Chloralhydrate(sedative hypnotic)

⚫ Volhard method:
⚫ is a kind of argentometric titration where the excess amount of
silver nitrate is back titrated by a known concentration of
ammoniumthiocyanate solution.
⚫ Application:
– Thiamine HCl
– Lindane
– Chlorbutol etc…..

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Hydrolysis by NaOH, and neutralization with sulfuric acid and the

titration of the so formed NaCl against AgNO3 using Mohr’s
method.

Chloral hydrate

Hydrolysis by NaOH, and neutralization with

nitric acid and the titration of the so formed NaCl
against AgNO3 using Volhard’s method.

Chlorobutanol

Hydrolysis by 7.5 M NaOH, and neutralization

with nitric acid and the titration of the so formed
NaBr against AgNO3 using Volhard’s method.
Bronopol

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Sodium amidotrizoate
Using the oxygen flask procedure to liberate free
halide salt (sodium iodide), and determination of
the iodide content precipitimetrically.

By direct Pptimetric determination by

using Hg(NO3)2 and ferric alum as
indicator

Benzylpenicillin potassium and all the

penicillin derivatives

Direct determination by Volhard’s method

Atropine bromide

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4- REDOX TITRATIONS

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⚫ Introduction:
⚫ The analytical procedures which are based on neutralization and
precipitation involve chemical reactions that take place without any
change in the valence of the reacting substances.
– On the other hand, oxidation – reduction method of analysis involve a
change in valence.
⚫ Oxidation: can be defined to involve any of the following:
– Addition of oxygen, such as SO2 + O → SO3
– Removal of hydrogen, e.g. H2S + O →H2O + S
– Increase in the oxidation state of a substance, e.g.
– Sn2+ + 2Cl- + 2HgCl2 → Sn4+ + 4Cl- + Hg2Cl2
– 2Fe2+ + 4Cl- + Cl2 → 2Fe3+ +6Cl-
– Loss of electrons

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⚫ Reduction: can be defined to involve any of the

following
– Addition of hydrogen e.g. CHCH + 2H → CH2 = CH2
– Removal of oxygen, e.g. CuO + 2H → Cu + H2O.
– Decrease in the oxidation state of a substance.
– Gain of electrons.
⚫ Oxidizing agent:
– is a substance responsible for oxidation of the other
substance in a redox reaction by undergoing reduction .
⚫ Reducing agent:
– is a substance responsible for reduction of the other
component in a redox reaction by undergoing oxidation.

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Redox indicators
⚫ These indicators undergo color change by being reduced or oxidized

OX .  RED.
(COLOR-1) (COLOR-2)

Example: 1, 10-Phenantrolline

Indicator Oxidized Reduced

Phenosafranine Red Colourless

Methylene blue Blue Colourless

Lndigotetrasulfonate Blue Colourless

(2,2-bipyridine) iron Pale blue Red violet

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REDOX APPLICATIONS
Examples for the most commonly used methods:
a) Titration with potassium permanganate:
b) Titration with potassium dichromate:
c) Titration with Cerium sulfate:
d) Direct titration with standard iodine solution:
e) Bromometric determinations:

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1. Titration involving potassium permenganate

⚫ The use of potassium permanganate (kMnO4) as an oxidizing
substance in acid solution depends up on the reactions expressed by
the following equations
MnO4–(aq) + 8H3O+(aq) + 5e– → Mn2+(aq) + 12H2O(l)
A. Preparation of 0.1N KMnO4 solution
⚫ Dissolve 3.3 gm of KMnO4 in 1000ml of water and boil the solution for
15 minutes ,allow it to stand for at least 2 days and filter through glass
filter.
Example: Assay of Ferrous Sulphate
⚫ Dissolve 1 gm of Ferrous Sulphate in 25ml of dilute H2SO4 and 25 ml
of water and titrate with 0.1N KMnO4 until a permanent pink color is
produced(each ml of the titrant is equivalent to 15.19 mg of FeSO4
and the volume of titrant consumed is 64.7 ml).
– Calculate the percentage strength of the drug.

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⚫ Soluton:
%C = titer value x volume of titrant consumed x 100
Sample taken
= 64.7 x 15.19 x 100
1000
=98.3%
2. Titrations using Ammonium Cerium sulfate Solution
⚫ A solution of Cerium Sulphate in dilute H2SO4 is a strong
oxidizing agent and considerably more stable than standard
KMnO4 solutions, provided sufficient H2SO4 is present to
prevent hydrolysis.
⚫ Although permanganate can be reduced to any of several
oxidation states,Ce3+ always results on reduction to Ce4+.

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Example. Determination of Ascornic Acid 300mg tablet.

⚫ An equivalent of 200mg of the powdered tablet, whose average
weight is 400mg, is dissolved in a mixiture of freshly boiled and
cooled water (80ml) and H2SO4 (10 ml) .
– It was then titrated with 0.1 N H2SO4 cerric sulphate solution and
consumed 9.7 ml .
– Calculate the amount of the powder taken.
– Calculate its percentage strength if its titer value is 20.5 mg
– Calculate the exact amount of ascorbic acid incorporated in a tablet
of ascorbic acid.
⚫ Solution:
⚫ 400mg=300mg
x = 200 mg
 x= 266.67 mg
⚫ % C = 9.7 X 20.5 X 100
200
=99.42 %

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⚫ c. 100 % = 300mg 99.42% =y

 y= 298.26 mg
⚫ Other applications:
– Ferrous fumarate
– Vitamin k
– Ferrous glucunate
3. Iodimetry and Iodometry titrations
⚫ Iodimetry:
– is a kind of redox titration in which an Iodine solution
of known concentration is used as a direct titrant.
I2 + 2 e-  2I- (Reduction)
– Substances which can be determined by this method are
reducing substances like sulphates and arsenites.
– I2 + 2NaS2O3 → 2 NaI +Na2S4O6( sodium tetrathionate)

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Indicator: Starch solution

⚫ Starch gives a colloidal dispersion of ß-amylose in hot
water ,which gives an intensely blue colored solution in
the presence of I2.
– But it must be added towards the end point of titration ,when
brown color is changed to straw color, because the reversibility
of the color is decreased in the presence of excess amount of
I2 solution.
⚫ Example: Determination of Dipyrone 50 %(w/v) injection.
– Procedure: Pipate volume of the injection solution equivalent to
500mg of dipyrone and titrate with 0.1N I2 solution till a blue
color persists for atleast 15 seconds .Each ml of the titrant is
equivalent to 17.57 mg of dipyrone and volume of titrant
consumed was 28 ml.
⚫ A . Calculate the volume to be pipated.
⚫ B. Calculate its percentage strength.

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⚫ Solution
50g=100ml
0.5 g= x
x = 1 ml
% C =28 ml x 17.57 x 100
500
=98.4 %

Other applications:
– Antymony sodium tertarate
– Dimercaprol

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⚫ Iodometry:
– is a redox titration method where I2 is not used as a
direct titrant .
– But a solution of KI is added to a solution of the
analyte .
– The productr are the reduced form of the analyte and
free I2 .
– The iodine liberated is proportional to the analyte
concentrationand is determined by back titrating it
with a titrant like sodium thiosulphate.

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Some redox applications

a) Titration with potassium permanganate:

COOH H3C CH OH
Oxalic acid Lactic acid
COOH COOH

b) Titration with potassium dichromate:

CH2OH
CH.OH Glycerol

CH2OH
c) Titration with Cerium sulfate:

Calcium
dobesilate

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d) Direct titration with standard iodine solution:

Benzylpencillin
potassium

Ascorbic acid Captopril

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e) Bromometric determinations:

Butylhydroxybenzoate Amylmetacresol
Benzylhydroxybenzoate

Chloroxylenol

Chlorocresol

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