COLLEGE OF PHARMACY

Valenzuela. Quezon City. Antipolo. Pampanga. Cabanatuan. Laguna

Pharmaceutical
Analysis 1
Day 9

Name of Instructor
College of Pharmacy
COURSE FACILITATOR DATE:
Complexometry or
Compleximetric
titrations
 Objectives
❖ Explain the principle used in Complexometric
titration

❖ Apply titrimetric techniques

❖ Discuss the difference between direct and residual

titration techniques and the importance of
performing blank determination

❖ Demonstrate ability in calculating the concentration

of active ingredients/samples using different
expressions of concentration.

❖ Interpret the results obtained from the analysis.

 OUTLINE
1. Complexation method
- Preparation of 0.05 M EDTA Solution

2. Hardness of water

3. Sample Problems
 COMPLEXATION
METHOD
❖ These titrations are used in the estimation of
metal salts.
❖ Complexometry (complex-formation method) is
the process based on the formation of a complex
substance in the course of analysis.
❖ Uses: Calcium, copper, mercury, magnesium,
zinc, aluminum and bismuth

❖ EDTA will react with metal ions to form a water-

soluble stable complex or a chelate compound
 What is EDTA?

❖ usual titrant used.

❖ it forms stable 1 : 1 complexes with all metals

except alkali metals such as sodium and
potassium.
 Complexometry cont

❖ When a metal ion combines with a molecule which

donate electrons, the resulting compound is termed a
complex.

❖ If the combining molecule contains two or more

groups that donate electrons, this complex is called a
chelate

❖ The groups bound to the central ion are called ligands

 Types of Ligands

NH3
❖ Ethane-1,2-diamine

1,4,7-triazaheptane
 Complexometry cont

❖ Stability constant - measure of the strength of the

interaction between the reagents that come
together to form the complex.

❖ Stability constants should be greater than 8.

❖ Li, Na forms very weak complex
❖ Ag and Ba Ks is below 8
❖ Fe and Cu colored metals
Stability constants (as log K) of
metal-EDTA complexes.

Mg2+ 8.7 Zn2+ 16.7

Ca2+ 10.7 Cd2+ 16.6
Sr2+ 8.6 Hg2+ 21.9
Ba2+ 7.8 Pb2+ 18.0
Mn2+ 13.8 Al3+ 16.3
Fe2+ 14.3 Fe3+ 25.1
Co2+ 16.3 Y3+ 18.2
Ni2+ 18.6 Cr3+ 24.0
Cu2+ 18.8 Na+ 1.7
 Stability with respect to pH of
some metal-EDTA complexes.
Minimum pH at Selected metals
which complexes
exist

1-3 Zr4+; Hf4+; Th4+; Bi3+; Fe3+

4-6 Pb2+; Cu2+; Zn2+; Co2+; Ni2+, Mn2+;
Fe2+; Al3+; Cd2+; Sn2+
8-10 Ca2+; Sr2+; Ba2+; Mg2+
Factors affecting EDTA
reaction
❖ Stability constant

❖ pH ( NaOH or ammonia-ammonium chloride

buffer TS)

❖ Interfering ions (cyanide, citrate, tartrate, fluoride

and other complex-forming agents)

❖ Neutral salts - NaCl

 Indicators
❖ Organic compounds which form colored
complex ions with metal ion in high dilutions.

❖ Qualities of a good indicator are

❖ sharpness of color change at the endpoint
❖ specificity of the indicator for the metal ion under
the conditions of the analysis
❖ stability constant smaller than that of the metal-
EDTA complex –i.e. the indicator must give up the
metal ion to the titrant EDTA for complexing and
not compete with it.
 Indicators
❖ Eriochrome black, Dithiazone and
Hydroxynaphthol blue.
❖ The indicator used is hydroxynaphthol blue for
Calcium containing compounds. ( deep blue)
❖ Zinc compounds and their preparations requires
Eriochrome black T.S. (red to blue)
 Standard Solution
❖ EDTA – disodium EDTA solution 0.05M

❖ Primary Standard: calcium carbonate

❖ Indicator: hydroxynaphthol blue (endpoint -

appearance of a deep blue color)

❖ Hexadentate ligand
 Complexometry cont

❖ Ionic bond O – Fe

❖ Coordinate bond N - Fe
 Preparation of
0.05 M EDTA Solution

Weigh accurately disodium edetate reagent

Dissolve in small amount of water
Transfer in VF
Dilute to volume with distilled water
Transfer into the appropriate container
 Complexometry cont

Molarity – no. of moles per liter of solution

g solute/ molar mass g solute

M = ------------------------------------------ = -----------------------

L of soln (molar mass) (L of soln)

M x Vol x Mol wt = grams

Direct Titration/ Residual
Titration
❖ Used for assay Ca, Mg and Zn
❖ Calcium chloride
❖ Zinc sulfate
❖ Ca in water or water hardness

❖ Used for assay of Al, Bi compounds

❖ Residual EDTA is determined using Metal-ion
solution (Zinc sulfate) and stable indicator
(dithiazone)
❖ Insoluble metal salts are estimated by back
titration; the sample is heated with excess EDTA
to form the soluble EDTA complex of the metal
and then the excess EDTA is titrated with salt
solutions containing Mg2+ or Zn2+ of known
concentration.

❖ Back titration with EDTA is used in the

pharmacopoeial assays of aluminium glycinate,
aluminium hydroxide, aluminium sulphate and
calcium hydrogen phosphate.
 Hardness of water
❖ Metal ions(minerals) that are dissolved in the
ground water

❖ Temporary and Permanent (Ca2+, Mg+2, Fe3+ and SO4-.)

❖ Measure of the capacity of the water to

precipitate soap
❖ Soap scum, clog pipe

❖ Parts per million (ppm)

 Hardness of Water
Rating Concentration of Calcium
Carbonate (mg/L)
Soft 0 to <75
Medium hard 75 to <150
Hard 150 to <300
Very hard 300 and greater

http://www.gov.calgary.ab.ca/cww/water
_quality/water_hardness/
 Complexometry cont

❖ A 50 mL water sample was determined for

hardness in terms of CaCO3. It required 40 mL of a
0.01-M EDTA solution for titration. Calculate the
total hardness in ppm. (mg/million)

❖ p153

❖ Nos. 4, 5
 Practice Problems
2. What volume of 0.05 M EDTA solution would be
equivalent to 100 ml of a 0.025 M solution of
titrable divalent cations?
 Practice Problems
3. How many grams of disodium
ethylenediaminetetraacetate is required to
prepare 250 ml of 0.025M solution? What would
the titer of this solution in terms of CaCl2.2H20,
MgSO4, ZnCl2?
 Practice Problems
4. A 200 mg pure CaCO3 was acidified and dissolved
in 500 ml of solution. A 50-ml sample required 25
ml of an EDTA solution for titration. Find the M
of the solution.
 Complexometry -
❖
Masking
The term used to indicate the determination of a
metal in the presence of another metal.

❖ This may proceed by adjusting the pH or with the use

of auxilliary complexing agents like
❖ Thioglycols – Zn-EDTA inactivates Hg, Cu, Bi
❖ TEA – imparts alkalinity Mg-EDTA over Al-EDTA
Fe, Al, Mn
❖ Potassium cyanide- mask Zn, Co, Ni, Cu
❖ Ammonium fluoride – Mg, Al, Ca
❖ Ascorbic acid, tartrates, citrates
 Masking
In a solution containing the following metals: Magnesium, Zinc,
Mercury, Aluminum and Copper

I. Mg III. Hg V. Mn

II. Zn IV. Al

1. Which of these metals may form complex with EDTA if the above
solution is treated with KCN?

2. If the sample will be treated with triethanolamine, which of

these metal/s will be precipitated?

3. Which of these metals will form a stable complex with EDTA at

pH of 4-6?

4. Which of these metals will not form complex with thioglycol?

 Sodium
Tetraphenylboron
❖ 6 5 4 Titrations
Na(C H ) B (freshly prepared,0.02M)
❖ Potassium dichromate by gravimetry

❖ Indicators: BPB

❖ Extraction Indicator- Chloroform

❖ Organic nitrogen compounds

❖ Alkaloids, amines, quaternary amine salts,
ammonium, potassium and silver ions
 Sodium Tetraphenylboron
Titration Cont.

R4N.Cl + Ind R4N.Ind + Cl

R4N.Ind + Na(C6H5)4B R4N.(C6H5)4B⇣ + Na

+ Ind
QACs
Related Links
Titration of water hardness (complexometry
explained).

❖ https://www.youtube.com/watch?v=akRcLMQUx
m4

EDTA Titration of Calcium and Magnesium

❖ https://www.youtube.com/watch?v=y8PskcAEdQ
4
 References
TEXTBOOK: Knevel, A.M. and Digangi, F.E., Jenkin’s Quantitative Pharmaceutical
Chemistry.USA: Mc Graw Hill. 1977.

REFERENCES:
• Watson, David G. Pharmaceuticals analysis: a textbook for pharmacy students and
pharmaceutical chemists, 4th ed. Singapore: Elsevier. 2017.
• Remington’s Pharmaceutical Sciences, (2013) Philadelphia: Lippincott William
and Wilkin
• WHO Expert Committee on Specifications for Pharmaceutical Preparations .
Geneva: World Health
• British Pharmacopeia . 2017.
• The United States Pharmacopeia(USP 40) : NF 35: The National Formulary
.Rockville, Md.: United States Pharmacopeial Convention. 2017.
• Handbook of Modern Pharmaceutical Analysis (2011) Amsterdam; Boston:
Academic Press/Elsevier
• Harris, D.C., Quantitative Chemical Analysis, 9th ed. New York : W.H. Freeman.
2015
 ANY
QUESTIONS?
You can find me at:
@fatima.edu.ph

facebook.com/
OLFUValenzuelaPharmacy/ (8)-661-3023 loc. 106