PHARMACEUTICAL
ANALYSIS
COMPLEXOMETRIC
TITRATIONwww.remixeducation.in
INTRODUCTION
A complexing agent is an electron donating ion or molecule (ligand)capable of forming one or more
covalent or co-ordinate bonds (dative bond)with metal ions. The complex thus formed has properties which are
differentfrom that of the metal ion. If a single bond is formed between a complexingagent and metal, then it is
called as a ligand. Such complexing agent isunidentate in nature and called as co-ordination compound.
If a complexing agent can form more than one bond with polyvalention, then it is considered as
polydentate and called as chelating agent.If the complex formed is soluble in water, then it is called as
sequesteringagent.
WERNER'S CO-ORDINATION NUMBER (WCN)
It is the number of small groups which can be attached to thecentral atom in a complex. This is no way
related to the valency of theton, but related to the steric factor or the space available for attachment.Elements
of the 2nd period can accommodate 4 groups, 3rd period - 6groups and 4th Period - 8 groups. A knowledge
of WCN is required toknow the maximum number of groups which can be accommodated arounda central ion.
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COMPLEXING AGENTS
The complexing agents are of different type which depends upon thefunctional group present.
1.They can be neutral molecules with lone pair of electron. Suchelectron donors such as S, O, N,
Halogens, groups like COOH, NH2and CN". eg. Ammonia forms cuprammonium complex with
copper.[Cu(NH3)4]2+ and (Cu(NH3)613+
2. Groups with easily replaceable protonCOOH, Phenolic & enolicОН. .3. Sequestering agents have
groups like COOH, SO3H, NH2 & OH. Dimethylglyoxime and Salicylaldoxime are examples for
chelating agents,where as EDTA or Ethylene Diamine Tetra Acetic acid is an example forsequestering
agent.
STRUCTURE OF COMPLEXING AGENTS
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EDTA is the most commonly used complexing agent or sequesteringagent which forms complex with divalent,
trivalent or tetravalent tons toform complexes. Irrespective of the valency of the lon, it forms 1:1 complexwith
ions. The number of rings formed depends upon the valency of the ion.
STRUCTURE OF COMPLEXES FORMED BY EDTA WITH POLYVALENT IONS
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STABILITY OF COMPLEX
The stability constant of a metal ion complex is given by K for theequation M + X → MX, where M is the
metal ion and X is the chelatingion. The square brackets represent the activities of the fons.
Stability constant (K) =[MX][M] [X]
The stability of the complex is decreased by acidic pH, increase intemperature and due to the presence of
electrolyte having no lon in commonwith the complex. The stability of the complex is increased by ethanoldue to
the suppression of ionisation.
EDTA (Edetic acid) ionises in four stages due to the presence of fourCOOH groups. i.e., PK1=2.0, pK2=2.67,
PK3=6.16 and pK4=10.26. Sinceedetic acid (EDTA) is less soluble in water, all pharmacopoeias specify theuse of
disodium edetate which is more soluble in water, in the place ofEDTA. In disodium edetate, two COOH groups are
present. Since pK4 is10.26, complexes formed from metal ion and disodium edetate are stableonly in alkaline
solutions. The most commonly used buffer is Ammonia -Ammonium chloride solution which has a pH of 10.5. At this
pH, thecomplexes formed are more stable and hence sharp end point can beobtained. (The greater the stability
of the complex, larger is the change infree metal ion concentration at the equivalence point and hence sharperthe
end point)
NEED FOR MAINTENANCE OF PH
• pH maintenance is required for two reasons.
1. pH affects the stability as well as the formation of the complex withmetal ion.
2. 2. Up to pH 10, PM Increases with pH. The colour of the indicator-metalion complex depends upon the PM,
which in turn depends on pH.TYPES OF DETERMINING END POINT IN COMPLEXOMETRIC TITRATIONS1.
Potentiometric method: Using suitable indicator electrodes,potentiometric method can be applied for
determining the end point.eg. Titration of iron and copper can be done by this method.
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TYPES OF DETERMINING END POINT IN COMPLEXOMETRIC
TITRATIONS
1. Potentiometric method: Using suitable indicator electrodes,potentiometric method can be applied
for determining the end point.eg. Titration of iron and copper can be done by this method.
2. Conductometric method: As there is sharp change in conductivityat the end point, polyvalent
lons can be titrated against EDTA. eg.Ca2+ Vs EDTA.
3. Amperometric method: Since polyvalent ions can be reduced,Amperometric titration can be
carried out by using Disodium edetate.The end point is determined graphically.
4. Spectrophotometric detection: There is change in the absorptionspectrum when a metal lon or a
complexing agent is converted tothe metal complex. Also when one complex is converted to
another,there is change in absorption spectrum even at low concentrationsuch as 0.001M. This
principle is used to detect end point. Theend point is shown by the sharp change in absorbance
marked bythe intersection of two lines.
5. Using PM indicators: The indicators used in complexometric titrationsare called as PM indicators,
since these indicators are responsiveto the concentration of the metal ions in solution. PM
indicatorsare chelating agents which give specific colour on the formationof complex with
metal ions. The free chelate and the complexwith metal ions have two different colours. Hence
based upon theconcentration of the metal ion, the colour of the indicator changesand so the end
point of such titration can be known.
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PM is the negative logarithm of metal ion concentration.
PM = -log (M)
The value of PM can be derived from the equation for stability constant.
K = [MX]
[M] [X]
then, [M] = [MX]
[X] K
Or log (M) = log [M X] - log K
[X]
and PM = log[X] - PK
[MX]
When (X) = (MX), -1.ely when there is equal activity of metal ion andcomplex is present,
PM = -PK or PM = pk.
PM INDICATORS USED IN COMPLEXOMETRIC TITRATIONS
The most commonly used indicators are:
1. Mordant Black II or Eriochrome Black T or Solochrome Black T
2. Xylenol orange
3. Murexide
4. Calcon mixture
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Structure of indicators
1. Mordant Black II: Free indicator is blue in colour (pH 10). Oncomplexation with metal ions, a
pink colour is formed. Below pH6.3 and above 11.5, it is reddish in colour. Hence it is used
atabout pH 10. It is used in the estimation of metal ions like Calcium,Magnesium, Zinc,
Cadmium, Manganese, Lead and Mercury.
2. It cannot be used either with oxidising ions like Ferric, Cerric andVanadate ions or with
reducing ions like Stannous and Titanous. Itcannot be used with ions like Copper, Aluminium,
Cobalt, Nickel,Silver, Titanium and Platinum as these ions form more stablecomplexes with
indicator than with chelating agent.
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2. Xylenol orange: It has yellow colour in acid solution and red colourin alkaline solution. The metal
complexes are red in colour. It isused in the estimation of Aluminium hydroxide gel, Aluminiumsulphate,
Aluminium hydroxide, Titanium dioxide and Zincundecylenate.
3. Murezide: (Ammonium purpurate) It is used in the estimation ofcalcium in the presence of magnesium. This
is because magnesiummurexide complex is less stable than calcium - murexide complex,
4. Calcon mixture: It is Sodium 2-hydroxy-1-(2-hydroxy-1- naphthylazo)naphthalene-4-sulphonate. It is
otherwise called as Solochrome Darkblue. It is used in the assay of Calcium carbonate and Calciumchloride.
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Other indicators are also occasionally used for specific titrations orother applications. They are Catechol violet,
Methyl thymol blue, Alizarineflourine blue, Sodium alizarin sulphonate, Diphenyl carbazone, Tiron(Disodium,
1,2-dihydroxyphenyl-3,5-disulphonate) and PAN (Pyridyl AzoNaphthol).
How does an Indicator in Complexometric Titration work?
In any titration,
Stability of Indicator-Metal complex < Stability of Chelate-Metal complex,
At the beginning of a titration, when indicator is added to metal ionsto be determined, the colour of the
contents of the flask is that of theindicator-metal complex. At the end point, when all the metal ions
havebeen complexed by the chelating agent, free indicator is liberated, whichhas a different colour. This
point only is called as the end point.
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TYPES OF COMPLEXOMETRIC TITRATIONS
1. Direct titration
2. Back titration
3. Replacement of one complex by another
4. Alkalimetric titration of metals
1. Direct titration
To a weighed amount of the substance to be estimated, measuredvolume of suitable buffer
solution and few drops of indicator is added.The contents are titrated against standardised disodium edetate
solutiontill the end point shown by the colour change. A blank titration is carriedout omitting the substance to be
determined, but contains all the othersolutions like buffer & indicator. The volume of edetate consumed in
blanktitration is subtracted from that obtained in the original estimation.
Examples of such estimation:
Bismuth - Nitrate, carbonate, oxynitrate, subnitrate
Calcium - Chloride, gluconate, lactate
Magnesium - Carbonate, oxide, stearate, sulphate, trisilicate
Zinc -Sulphate, oxide, undecenoate
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2. Back titration
Back titration is necessary in the following cases:
- metals which are precipitated as hydroxides in the pH used
- for insoluble substances like Lead sulphate, Calcium oxalate
- those react slowly with disodium acetate
- those form stable metal chelate complex than with indicator
# Method:
In this method, a known excess of disodium edetate, buffer solutionand few drops of indicator is added. The
complexation is favoured byheating, then cooled and the excess edetate is back titrated againstmagnesium sulphate or
zinc sulphate.
# Example
Alum: KAl(SO4)2. 12H20
Aluminium Hydroxide gel, dried aluminium hydroxide gel
Calcium phosphate
3. Replacement of one complex by another
When sharp end point is not obtained by director back titration,this method is followed. In this method, the metal
ion is determined bydisplacement of an equivalent amount of magnesium or zinc from lessstable edetate complex. The
liberated ions are titrated against edetate.
M2++ Znx2-→ MX2-+ Zn2+
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Example: Cadmium, lead and mercury can be determined by this method.
4. Alkalimetric titration of metals
Mn+ + H2x2- → MX (n-4) + 2H+
When a polyvalent ion is added to a complex, protons are liberated.This acidity is quantitatively titrated
with an alkali but in an unbuffered solution. An acid-base indicator itself is sufficient, instead of pM
indicator.Alternatively potentiometric method of determining end point can also be done.
MASKING AND DEMASKING AGENTS
Masking and demasking agents are those which precipitate or complexfons selectively, in
order to estimate a specific ion.
Need for masking or demasking agents
1. EDTA as well as its salt, disodium edetate forms complexes withseveral metal ions. During estimation of a
specific ion, other ſonicimpurities also are estimated. This gives false values.
2. 2. Sometimes when two or more ions are to be estimated in a mixture,each ion has to be selectively
titrated.For the above reasons, masking and demasking agents are required.
This can be done by any one of the three methods:
1. Addition of precipitants
2. Addition of complexing agents
3. pH control
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1. Addition of precipitants: When interference due to the followingionsare encountered, the precipitants
are added, collected asprecipitates and then estimated separately. In some cases, filtrationis not necessary.
The estimation of analyte ion is not affected dueto slow reaction of edetate with these insoluble complexes.
2. Addition of complexing agents: Addition of these complexing agentscauses formation of complexes
with interfering tons. These complexesare more stable than the edetate complexes and thus elimination
ofimpurities and selective titration can be done easily.
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3. pH control: The edetate complexes with alkaline earth metals arenot stable below pH 7. But in this pH
region and upto pH 3,complexes with Tin (Sn4+), Iron (Fe3+). Cobalt (C03+) and Thorium(Th4+) are stable
and can be selectively titrated by varying pH.
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Preparation of 0.05M disodium edetate
Dissolve 18.6g of disodium ethylene diamine tetetracetate in sufficientwater to produce 1000ml
and standardise the solution.
Standardisation of 0.05M disodium edetate
Method 1
Weigh accurately 1.251g of calcium carbonate and transfer into a250ml standard flask. Add minimum
quantity of dilute hydrochloric acidto dissolve the calcium carbonate, by boiling off the carbondioxide.
Cooland make upto volume with distilled water. Pipette out 20ml of this solutionin to a conical flask, add
5ml of Ammonia Ammonium chloride bufferand few drops of Calcon mixture as indicator (alternatively,
Modernt BlackII mixture or Eriochrome Black Tor Solochrome Black T can be used).The contents of the flask
are titrated against 0.05M disodium edetate (TV),until pink colour changes to full blue colour of the
indicator. A blanktitration is performed with only buffer and indicator and the volume ofedetate (BV) is
subtracted from that obtained in the first titration.
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Strength of 0.05M disodium edetate = Wt. of Calcium carbonate x 20
(TV - BV) 0.005004 250
Method 2
Weigh accurately about 0.8g of granulated zinc P.S., dissolve by gentlewarming in 12ml of dilute hydrochloric acid and
five drops of brominewater. Boil to remove excess bromine, cool and add sufficient water toproduce 200ml. Pipette
20ml of the resulting solution into a flask andnearly neutralise with 2N sodium hydroxide. Dilute to about 150ml
withwater, add sufficient ammonia buffer pH 10 to dissolve the precipitate andadd 5ml in excess. Add 50mg of
mordant black 11 mixture and titratewith the disodium ethylenediamine tetraacetate solution until the solutionturns
green. Each 0.003269g of granulated zinc is equivalent to lml of0.05M disodium ethylenediamine tetraacetate.
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Note:
In the titration of calcium gluconate, calcium lactate and calciumlevulinate, 5ml of 0.05M Magnesium
sulphate is added to get sharp endpoint. This is because the release of Mg2+ from Mg2+ -indicator
complexis faster than the release of Ca2+ from Ca2+ -indicator complex Ifmagnesium sulphate is
not added, there will be overshooting of the endpoint and so correct end point is not obtained. If
magnesium sulphate isadded, towards the end point, edetate abstracts Ca2+ slowly. But at theend
point, edetate abstracts Mg2+ suddenly. This causes a clear transitionin colour. Hence the end point is
sharp. It should also be noted thatStability of metal – Indicator complex < Stability of metal -
edetate complex.
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