quantitative analysis of antihisatminics

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Guided By:
Keyur B. Ahir
Falgun a mehta
Prepared By:
Shweta singh
M.Pharm (Sem - II)
Indukaka Ipcowala College Of Pharmacy.

2.  Cetirizine Hydrochloride
 Diphenhydramine Hydrochloride
 Cyproheptadine Hydrochloride
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Cetirizine
Hydrochloride
Description: A white or almost white powder.
•Principle: Potentiometry
A convenient and useful method of determining the
equivalence point of a titration, i.e. the point at which the
stoichiometric analytical reaction is complete.

4.  If an indicator electrode is sensitive to the concentration of the
chemical, undergoing titrimetric reaction, and a reference
electrode, whose potential is not sensitive to any dissolved
chemical in solution, are immersed in the solution under
examination to form a galvanic cell, the potential difference
between the electrodes may be sensed by potentiometer
 If a graph of the variation of potential difference is plotted as a
function of the quantity of the titrant added, a sigmoid curve
results with a rapidly changing portion in the vicinity of the
equivalence point. The mid- point of this linear vertical
portion or the inflection point may taken as the end-point of
the titration.
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•Assay
• Weigh accurately about 0.1 g, dissolve in 70 ml of a
mixture of 30 volumes of water and 70 volumes of
acetone.
• Titrate with 0.1 M sodium hydroxide to the second point
of inflexion.
• Determine the end-point Potentiometrically .
• Carry out a blank titration.
• 1 ml of 0.1 M sodium hydroxide is equivalent to
0.01539 g of C21H27Cl3N2O3.

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Cetirizine Tablets
•Principle: Determine by liquid chromatography
The principle of liquid chromatography is a separation
process based on distribution between two phases, where the
sample components is propelled by liquid which percolates a
solid stationary phase.
Thus a variety of liquids and stationary phases can be
used in liquid chromatographic systems. Bonded phase
chromatography (BPC) or liquid solid chromatography (LSC)
have the largest impact in the field of liquid chromatography
today and older techniques such as liquid-liquid
chromatography (LLC) have been replaced.

7.  The liquid chromatographic process and thereby the separation
of sample components may be achieved both in low and high
pressure systems. Appropriate selection of the separation
mode, stationary phase and mobile phase may be normal
phase, reversed phase, size-exclusion (SEC) or ion-exchange
(IEC) liquid chromatography.
• Procedure:
• Test solution: Weigh and powder 20 tablets. Weigh accurately
a quantity of the powder containing about 25 mg of Cetirizine
Hydrochloride, add the mobile phase, mix and dilute to 50.0
ml with the mobile phase, filter. Dilute 1.0 ml of the solution
to 10.0 ml with mobile phase.
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•Reference solution: A 0.05 per cent w/v solution of
cetirizinehydrochloride RS in the mobile phase. Dilute 1.0 ml of
the solution to 10.0 ml with the mobile phase.
•Chromatographic system
A stainless steel column 25 cm x 4.6 mm, packed with
octadecylsilane chemically bonded to porous silica (5μm),
•Mobile phase: dissolve 0.19 g of heptane sulphonic acid
sodium salt in 300 ml water add 700 ml acetonitrile and mix.
Adjust pH to 3.2 with 0.05 M sulphuric acid, filter.
•Flow rate. 1.2 ml per minute.
•Spectrophotometer set at 230 nm,20 μl loop injector. Inject
the reference solution. The test is not valid unless the tailing
factor is more than 2.0, the column efficiency in not less than
2000 theoretical plates and the relative standard deviation for
replicate injections is more than 2.0 per cent.
Inject alternatively the test solution and the reference solution.
•Calculate the content of C21H27Cl3N2O3 .HCl in the tablet

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Diphenhydramine
Hydrochloride:
•Principle: Non aqueous titration
Non aqueous titration is the titration of substances
dissolved in non-aqueous solvent. It is the most common
titrimetric procedure used in pharmacopoeial assays and
serves a double purpose:
• It is suitable for the titration of very weak acids and
very weak bases, and
• It provides a solvent in which organic compounds are
soluble.
The most commonly used procedure is the titration of
organic bases with perchloric acid in anhydrous acetic acid.

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•Substances which are either too weakly basic or too weakly
acidic to give sharp endpoints in aqueous solution can often be
titrated in non-aqueous solvents. The reactions which occur
during many non-aqueous titrations can be explained by means
of the concepts of the Bronsted-Lowry theory.
•According to this theory an acid is a proton donor, i.e. a
substance which tends to dissociate to yield a proton, and a
base is proton acceptor, i.e. a substance which tends to
combine with a proton. When an acid HB dissociates it yields
a proton together with the conjugate base B of the acid:
•HB ⇌ H+ + B- acid proton base alternatively, the base B will
combine with a proton to yield the conjugate acid.
•HB of the base B, for every base has its conjugate acid
and, every acid has its conjugate base.

11. • Assay
 Weigh acc. about 0.5 g, dissolve in 20 ml of anhydrous glacial
acetic acid and add 10 ml of mercuric acetate solution. Titrate
with 0.1 M perchloric acid, crystal violet solution as indicator.
Carry out a blank titration.
 1 ml of 0.1 M perchloric acid is equivalent to 0.02918 g of
C17H21NO.HCl.
DIPHENHYDRAMINE CAPSULES
Principle: Acid base titration
 An acid-base titration is the determination of the
concentration of an acid or base by exactly neutralizing the
acid/base with an acid or base of known concentration. This
allows for quantitative analysis of the concentration of an
unknown acid or base solution.
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The equivalence point of the reaction, the point at which
equivalent amounts of the reactants have reacted, will have a pH
dependent on the relative strengths of the acid and base used.
The pH of the equivalence point can be estimated using the
following rules:
• A strong acid will react with a strong base to form a neutral
(pH=7) solution.
• A strong acid will react with a weak base to form an acidic
(pH<7) solution.
• A weak acid will react with a strong base to form a basic
(pH>7) solution.

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•When a weak acid reacts with a weak base, the equivalence
point solution will be basic if the base is stronger and acidic if
the acid is stronger. If both are of equal strength, then the
equivalence pH will be neutral.
However, weak acids are not often titrated against weak bases
because the color change shown with the indicator is often
quick, and therefore very difficult for the observer to see the
change of color.
•The point at which the indicator changes color is called the end
point. A suitable indicator should be chosen, preferably one
that will experience a change in color (an end point) close to
the equivalence point of the reaction.

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Cyproheptadine
Hydrochloride
Description. A white or slightly yellow, crystalline powder
•Principle: Non aqueous titration
Non aqueous titration is the titration of substances
dissolved in non-aqueous solvent. It is the most common
titrimetric procedure used in pharmacopoeial assays and
serves a double purpose:

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• It is suitable for the titration of very weak acids and
very weak bases, and
• It provides a solvent in which organic compounds are
soluble.
The most commonly used procedure is the titration of
organic bases with perchloric acid in anhydrous acetic acid.
•Assay:
Weigh accurately about 0.5 g, dissolve in 0.5 ml of
acetic anhydride and 20 ml of anhydrous glacial acetic acid and
add 10 ml of mercuric acetate solution.
Titrate with 0.1 perchloric acid, using crystal violet
solution as indicator.
Carry out a blank titration.
1 ml of 0.1 M perchloric acid is equivalent to 0.03239 g of
C21H21N,HCl.

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CYPROHEPTADINE SYRUP
•Principle: U.V. Spectrometry
It follows beer lamberd ‘s law . It states that when
monochromatic light passes through the sample the amount of
light absorbed is proportional to the concentration of the
analyte, path length.
A=abc;
Where, a- Absorptvity
b- path length
c – concentration
•Procedure:
To an accurately measured volume of the syrup containing
about 2 mg of Cyproheptadine Hydrochloride add 20 ml of a 1
per cent w/v solution of sodium bicarbonate and extract with
two quantities, each of 25 ml, of 2,2,4- trimethylpentane.

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•Wash the combined 2,2,4- trimethylpentane extracts with 5
ml of the sodium bicarbonate solution and discard the
washings.
•Extract the 2, 2, 4-trimethylpentane solution with 50 ml of
0.05 M sulphuric acid and collect the aqueous extract in a
100-ml volumetric flask.
•Dilute to volume with 0.05 M sulphuric acid and mix.
Filter a portion of the solution through a dry filter paper
and discard the first 20 ml of the filtrate.
•Measure the absorbance of the filtrate at the maximum at
about 286 nm using 0.05 M sulphuric acid as the blank.
•Calculate the content of C21H21N, HCl taking 355 as the
specific absorbance at 286 nm.

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CYPROHEPTADINE TABLETS
•Principle. U.V Spectrometry
It follows beer lamberd ‘s law . It states that when
monochromatic light passes through the sample the amount of
light absorbed is proportional to the concentration of the
analyte , path length .
A=abc,
Where, a- Absorptvity
b- path length
c – concentration
•Assay:
•Weigh and powder 20 tablets.

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•Weigh accurately a quantity of the powder containing about
1.5 mg of Cyproheptadine Hydrochloride, add sufficient
ethanol (95 per cent) to produce 100.0 ml, mix well and filter.
•Measure he absorbance of the filtrate at the maximum at
about 286 nm.
•Calculate the content of C21H21N,HCl taking 355 as the
specific absorbance at 286 nm.

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•REFERENCE:
• Government of India Ministry of Health and Family
Welfare Indian pharmacopeia 2007 and 2010; published
by the controller of publications Delhi.
• Vogel’s Textbook of Quantitative Chemical Analysis;
Fifth Revised Edition; G.H.Jeffery, J.
Bassett, R.C.Denney; , published by Longman scientific
& technical, England.

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