1

Principle and Procedure Involved In Quantitative

Analysis of Antihistamines

Guided By: Keyur B. AhirFalgun a mehta

Prepared By:Shweta singh

M.Pharm (Sem - II)Indukaka Ipcowala College Of Pharmacy.

2

Cetirizine Hydrochloride

Diphenhydramine Hydrochloride

Cyproheptadine Hydrochloride

Contents:

3

Cetirizine Hydrochloride

Description: A white or almost white powder.

•Principle: PotentiometryA 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.

5

•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.

6

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.

8

•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

9

Diphenhydramine Hydrochloride:

•Principle: Non aqueous titrationNon 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.

10

•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 CAPSULESPrinciple: 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.

12

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.

13

•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.

14

Cyproheptadine Hydrochloride

Description. A white or slightly yellow, crystalline powder

•Principle: Non aqueous titrationNon 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:

15

• 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.

16

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.

17

•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.

18

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.

19

•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.

20

•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.

21