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DROTAVERINE HYDROCHLORIDE METHOD OF ANALYSIS

Specifications
S. No.

01.

Test

Description

Specification

Light Yellow or greenish yellowish crystalline


Powder. Almost with out odour

02.

Solubility

Moderately soluble in water, soluble in


Alcohol (96%), Easily Soluble in Chloroform

03.

Identification
a)

By IR

IR spectrum is concordant with working


Reference standard.

b)

BY UV spectrum

UV Spectrum is concordant with working


reference standard.

c)

By chloride reaction

Passes.

and with FeCl3


4)

Melting Point

About 2100C
(with decomposition 205C-215C)

5)

Clarity of the solution

Clear or not more than reference solution

6)

Colour of solution

Not more intensive than reference standard

07)

Between 3.50 - 5.50

08)

pH
(1.0 % Aq. solution)
Foreign impurities by TLC

09).

Water content by KF

Not more than 2.00% w/w.

10).

Loss on drying

Not more than 5.00% w/w

Not more than 1.00%

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DROTAVERINE HYDROCHLORIDE METHOD OF ANALYSIS

11).

Sulphated Ash

Not more than 0.20 %w/w.

12).

Heavy metals

Not more than 20ppm.

13)

Sulphates

Not more than 0.05%w/w

14).

Assay

Between 98.0 % - 101.0% w/w

(Non aqueous titration)


Method Of Analysis
01.

Description :

Take about 1 g of the test sample in a watch glass and observe visually with black
back ground.

The material should be Light Yellow or greenish yellow crystalline power, almost
with out odour.

02.

Solubility :

a.

Take about 1 g of the test sample into a 50 mL glass-stoppered cylinder and add 10
mL of Chloroform and mix well.

The resultant solution should be clear and with out any suspended particles.

b.

Take about 1 g of the test sample into a 50 mL glass-stoppered cylinder and add 30
mL of Alcohol (96%) and mix well.

The resultant solution should be clear and with out any suspended particles.

Take about 0.1 g of the test sample into a 50 mL glass-stoppered cylinder and add 10
mL of water and mix well.
The resultant solution should be clear and with out any suspended particles

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DROTAVERINE HYDROCHLORIDE METHOD OF ANALYSIS

03.

Identification :

a.

By IR :

Apparatus : Infrared spectrophotometer.

Test sample preparation:

Weigh accurately about 200 mg of KBr, previously dried at 250C and cooled, into a
mortar and grind to a fine powder.

Add about 5 mg of test sample, mix perfectly and grind to a uniform powder.

Take a small quantity of the powder and prepare a thin semi-transparent disk.

Record the IR spectrum of the disk from 3700 sm-1 to 400 sm-1 taking air
as reference.
Standard preparation :

Weigh accurately about 200 mg of KBr, previously dried at 250C and cooled, into a
mortar and grind to a fine powder.

Add about 5 mg of working reference standard, mix perfectly and grind to a uniform
powder.

Take a small quantity of the powder and prepare a thin semi-transparent disk.

Record the IR spectrum of the disk from 3700 sm-1 to 400 sm-1 taking air
as reference.
Specification : The Infra red absorption spectrum is concordant with working
reference standard,.

b)

By UV Spectrum

Accurately weigh about 0.075 gm of the sample in to a 100ml volumetric flask


dissolve in 0.1M solution of hydrochloric acid and make up volume up the marking
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with same solvent.

Take 2 ml of the above solution in to 100ml volumetric flask and make up to 100 ml
with 0.1M hydrochloric acid.

Check the above solution (15mcg/ml) by UV in the wave lengths between 220 to
400 nm. in the ditch with layer thickness 1sm Should exhibit maximums at
241 1nm, 302 2nm and 353 2nm.

Use 0.1M solution of hydrochloride as blank.

c)

By chloride Reaction and with FeCl3:


I.

Chloride :

REAGENTS :

2M nitric acid.
4.25% v/v silver nitrate solution R.
10M ammonia.
Potassium dichromate
Sulphuric acid
Diphenylcarbazide solution
PROCEDURE

Method - A :

Dissolve a quantity of the substance being examined containing about 2 mg of


chloride ion in 2 ml of water or use 2 ml of the prescribed solution.

Acidify with 2M nitric acid, add 0.4 ml of silver nitrate solution R, shake and allow
to stand.

A curdy, white precipitate is produced. Centrifuge and wash the precipitate with three
1- ml quantities of water. Carry out this operation rapidly in subdued light,
disregarding the fact that the supernatant solution may not become perfectly clear.

Suspend the precipitate in 2 ml of water and add 1.5 ml of 10M ammonia.

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DROTAVERINE HYDROCHLORIDE METHOD OF ANALYSIS

The precipitate dissolves easily with the possible exception of a few large particles
Which dissolve slowly.

II
Dissolve about 0.01gm of the test sample in a 5ml of concentrated sulphuric acid,
add 1 drop of 0.1M solution of trichloric ferrum.

Heat the solution at 1000C during 3 minutes.

A green colouring is appers.

After cooling add 1 drop of 2M solution of nitric acid.

Brownish-red colouring is formed (difference from papaverine, which becomes


purple at the beginning)

4)

Melting point

Apparatus : MP apparatus

Reduce about 1 gram of the sample to a fine powder in a mortar.

Pack the capillary tube with sample by tapping on a solid surface so as to form a
Tightly packed column of about 3.5 mm in height

Heat the oil bath in the melting range apparatus by turning ON the heating knob

Heat the oil bath to about 190C. Regulate the rate of raise of temperature to
1 2C per minute.

Insert the capillary tube in to apparatus, when the temperature of the bath reaches
200C

Observe the temperature at which the column of the sample in the capillary tube
collapses definitely against the side of the tube and the temperature at which the
sample becomes liquid throughout.

Specification : The melting point of the test sample about 2100C (with decomposition between
205C and 215C

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DROTAVERINE HYDROCHLORIDE METHOD OF ANALYSIS


05)

Clarity of solution:

Take 0.5 gm of test sample and dissolve in 50ml of water in to a nesslar cylinder.

Check the clarity of the solution. The solution should be clear.

06)

Colour of solution:
Test preparation: Take 0.5 gm of test sample and dissolve in 50 ml of water.
Preparation of Reference solutios:
I. Solution of Cobalt chloride: 60 mg of COCl 6H2O in 1m of 0.1M solution of
sulphuric acid
II. Solution of Copper sulphate: mg CuSO4 5H2O in 1ml 0.1M solution of sulphuric
acid.
III. Solution of Potassium dichromate: 4.9mg K2Cr2O7 in 1 ml 0.1M solution of
Sulphuric acid.

IV Solution of Chloric (III) Ferrum: 45mg FeCl3 6H2O in 1ml 0.1M solution of
sulphuric acid.
For obtain reference G(green) mix 3.5ml(I), 20.1ml(II), 10.4ml(III), 4.0ml(IV)
solutions in volumetric flask accommodating 100ml and drive the solution volume
Up to the marking with 0.1M solution of sulphuric acid.
For obtaining reference G5 mix 25.5 ml of reference G and 75ml of 0.1M sulphuric
acid solution.
For obtaining reference Y (yellow) mix 9.5 ml of reference I and 1.9 ml of reference
II and 10.7ml of reference III and 4.0ml of reference IV in volumetric flask and
make up to 100 ml with 0.1M sulphuric acid solution.
For obtaining reference Y5 mix 25.5ml of reference Y and 75 ml of 0.1M sulphuric
acid solution.
Compare the test sample solution with reference solutions G5 or Y5 .
The intensity of the test sample should not more than the intensity of G5 or Y5

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07.

pH (1.0% Aq. solution) :

Apparatus : pH meter

Weigh accurately about 1 g of test sample into 100 mL volumetric flask

Dissolve in and make up to the volume with water and mix well.

Transfer the prepared test solution into a 100 mL beaker for examination of pH.

Examine the pH of the test solution and note down the result.

pH of the test sample solution should be between 3.50 and 5.50.


Specification:
pH of the 1.0 % test sample solution in water should be between 3.50 and 5.50

08)

Foreign impurities by TLC


Solution A: Take 0.1 gm of test sample in to 10ml volumetric flask dissolve it in
chloroform and dilute to 10 ml with the same solvent.
Solution B: Take 1ml of above solution(A) in to 100ml volumetric flask and dilute
with the same solvent up to the mark.
Procedure:
Apply 10l of solution A and 5 & 10 l of solution B on the star line of plate
10X20cm Kieselgel G activated at 1100C during 1 hour.
Saturate chromatographic chamber for 1 hour with a mixture of solvents
Xylene-Methyl ethyl ketone- Methanol-Diethylamine in the ratio of (20:20:3:1)
Place the plate and chromatograph by ascending method. When the solvent front
passes 15cm, take the plate out of the chamber, dry first at room temperature, the in
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drying oven at 1050C during 5 min. Examin chromatogram in UV light at
wavelength 366nm. Spot of the preparation has blue coloring, Rf value about 0.50.6. Total content of impurities evaluated by totality of size and colour intensity of
spots on chromatogram of the preparation in comparision with spots on the
chromatogram of the witness (Solution B), must not exceed 1.0%.
09.

Water content by KF:

Apparatus : KF apparatus

Fill the burette with K.F reagent with the help of the rubber bellow.

Fill the titration vessel with 30 to 40 mL of methanol.

Switch on the instrument.

Rotate the stop cock to half open position and press the start button.

Stop the button when the sound of siren is heard.

Note down the initial burette reading (I).

Weigh accurately and transfer about 0.2 g of the test sample (W) into the titration
vessel.

Switch on the start button.

Note down the final burette reading (F) when the sound of siren is heard.

Calculate the water content of the test sample by the following equation.
Water content, % w/w

(F I ) x K.F Factor x 100


W x 1000

Specification : The water content by KF of the test sample should not more then 2.0% w/w.
Note : 1.
2.

Determine the Moisture content as an average of two trials.


The difference between two trials should not be more than 0.10
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3.

Average should not be done in case any of the trials fails.

10.

Loss on drying :

Apparatus : Vacuum Oven

Weigh accurately about 1 g of the test sample and transfer it to a weighing bottle
of weight W1 with a stopper previously dried at 120 + 2OC for 30 minutes.

Note down the weight of the weighing bottle with the test sample (W2).

Find out the weight of the test sample taken , ( W2 - W1 ).

Distribute the sample evenly in the weighing bottle by sidewise shaking to a


height of about 5 mm

Place the weighing bottle uncovered at 80 + 2oC in an Vacuum oven for 3 hours,
leaving the stopper also in the oven.

After 3 hours, open the Vacuum oven and immediately place the stopper on the
weighing bottle.

Place the weighing bottle in a desiccator to reduce the temperature to room temperature.

Determine the weight of weighing bottle with the contents.

Note down the weight (W3).

Find out the loss of test sample after drying, ( W2 W3 ).

Calculate loss on drying with the following formula.


Loss on drying % w/w

( W2 W3 ) x 100
( W2 - W1 )

Specification :
The Loss on drying of the test sample should not be more than 5.0% w/w.
11.

Sulphated Ash :

Apparatus : Muffle furnace

Weigh accurately about 0.5 g of test sample and transfer to a platinum crucible of
weight W1, previously ignited at 800C for 30 minutes, cooled in a desiccator.

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Note down the weight of the crucible with the test sample W2.

Find out the weight of the test sample taken, W , (W2 -W1)

Moisten the test sample with 1 mL of sulphuric acid.

Heat gently at first, until the sample is thoroughly charred.

Cool the residue and moisten with 1 mL of sulphuric acid and heat gently until
white fumes no longer evolve.

Ignite at 800oC in a muffle furnace until the carbon is consumed.

Place the crucible in a desiccator, cool and weigh the crucible with residue (W3).

Find out the weight of the residue, (W3 - W1).

Calculate the Residue on ignition as follows.


Calculation :
Weight of the Platinum Crucible

= W1

Weight of the Crucible + Test Sample

= W2

Weight of the Test Sample taken (W)

= (W2 -W1)

Weight of the Crucible + Residue

= W3

Weight of the residue

Residue on ignition %w/w

= Weight of the Residue X 100

(W3 - W1)

Weight of the Test Sample

= (W3 - W1) x 100


W
If the residue content is not meeting the specification, continue moistening the
residue with sulphuric acid, heating and ignition until consecutive weighings do not
differ by more than 0.50 mg per g of the test sample taken. Determine the final
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weight Wn
Weight of the Crucible + Residue
=
(after incineration to constant weight)

Wn

Weight of the residue

( Wn - W1)

Residue on ignition %w/w

= Weight of the Residue X 100


Weight of the Test Sample
=

( Wn - W1) x 100
W
Specification : The Sulphated ash of test sample should not be more than 0.20 % w/w.
12.

Heavy Metals:
Preparation of Standard Lead Solution:

Pipette out 10 mL of the Lead Nitrate Stock Solution to a 100 mL volumetric flask.

Dilute the above solution to 100 mL with water.


Standard Preparation :

Pipette out 4mL of Standard Lead solution to a 50 mL test tube.

Add 10 mL of 6N Hydrochloric acid .


Test Preparation :

Weigh accurately about 2 g of the test sample in to a crucible.

Add Sulphuric acid to wet the test sample.

Ignite the mixture at a low temperature until it is thoroughly charred.

Add 2 mL of Nitric acid and 5 drops of Sulphuric acid to the carbonized mass.

Ignite the contents in a muffle furnace at 500 to 600OC until the carbon is
Completely burned.

Cool the mass and add 5 mL of 6N Hydrochloric acid.

Cover and digest over a steam bath / water bath for 10 minutes.
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Cool and transfer the solution to a test tube.

Rinse the crucible with 5 mL of 6N Hydrochloric acid, and transfer the rinsing to the
test tube.
Monitor Preparation :

Pipette out 4mL of Standard Lead solution in to a crucible.

Weigh and transfer 0.2 g of test sample in above crucible.

Evaporate on a steam bath / water bath the above mixture to dryness.

Ignite at the same time, in the same muffle furnace ,and under the same conditions
used for the Test preparation.

Cool the mass and add 5 mL of 6N Hydrochloric acid.

Cover and digest over a steam bath / water bath for 10 minutes

Cool and transfer the solution to a test tube.

Rinse the crucible with 5 mL of 6N Hydrochloric acid, and transfer the rinsing to the
test tube.
Procedure:

Adjust the pH of the solutions in each of the tubes containing the standard
preparation, the test preparation, and the monitor preparation with ammonium
hydroxide by cautiously and dropwise to 9 .

Cool, and adjust the pH of the solutions in each of the tubes with glacial acetic acid add
dropwise to 8.

Add 0.5 mL of glacial acetic acid to each of the tubes.

The pH of the solutions to between 3.0 and 4.0 with1N acetic acid or 6N Ammonium
hydroxide
using short range pH indicator paper as external indicator.

Dilute the contents to 40mL with water. (each of the tubes)

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Comparison:

Add 10mL of freshly prepared hydrogen sulphide solution to each of the test tubes
containing the standard preparation, the test preparation, and the monitor preparation
and mix.

Allow the each preparations to stand for 5 minutes.

Compare the three solutions by viewing downwards over a white surface


Specification:
For Test preparation

The colour of the solution from the test preparation is not darker than that of the
solution from the standard preparation.
For Monitor Preparation

The colour of the solution from the monitor preparation is equal to or darker than that
of the solution from the Standard Preparation .

13.

Sulphates:
Test preparation:
Use 50ml identical test tube for test preparation and reference preparation. Dissolve
about 1.0g of the substance in 10ml of distilled water. Shake this solution with 5.0ml
of sulphate reagent and evaluate after 10 min. by comparison with the
simultaneously prepared test with the solution of comparison.
Reference preparation:
Shake 10ml of distilled water with 2.0ml of sulphate reagent. Acidify with 1 ml of
2M HCl and add 1.0 ml of 100g/ml sulphate limit test solution.
Observe the turbidity and record the results. Turbidity of test preparation shall not
be more than that of reference preparation.

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Preparation of 100g/ml sulphate limit test solution:


Dissolve 18.2 g of potassium sulphate in distilled water and complete the volume to
1000ml. Dilute 1.0ml of this solution to 100ml with distilled water.
Preparation of Sulphate reagent:
Mix 5 ml of the sulphate limit test solution with 7.5 ml of 96% ethanol. Shake
thoroughly and let stand the mixture for 2-3 minutes.

14.

Assay (Non Aq. Titration) :

Apparatus :Pipette, Burette

Chemicals :
Glacial Acetic acid

AR grade.

Mercuric acetite

AR grade.

Crystal Violet

AR grade

0.1N Perchloric acid


Procedure

Take a clean 100 mL Conical Flack

Weigh accurately about 0.20 g of test sample into above flask and note down
the weight of the test sample taken, W gram.

Add 10ml of Glacial Acetic acid and 5.0ml of 3%solution of Mercuric acetate(II) in
glacial acetic acid.

Add 1-2 drops of Crystal violet indicator solution

Fill the burette with 0.1N Perchloric acid solution

Swirl the conical flask to dissolve the contents and cool it to room temperature.

Note down the initial burette reading ( I ).

Titrate the contents of the flask with 0.1N Perchloric acid solution until the
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colour of the solution changes from blue to emerald green which indicates the
end point.

Conduct the blank by the same manner with out sample.

Note down the final burette reading (F). The difference between (F) and (I) gives
the volume, in mL of 0.1N Perchloric acid solution consumed by the test sample
(TV).

Calculate the assay on Dryed basis of the test sample using the following formula
TV X N of 0.1 N Perchloric acid X 0.43397 X 100 X 100
W x (100- Loss on drying of the test sample)
Where,
W = Weight of test sample taken in g.
T.V = (F- I) = Volume, in mL of 0.1N Perchloric acid solution consumed in the
titration.
N

= Normality of 0.1N Perchloric acid solution used in the titration.

Specification :
Assay (non aqueous titration) of the test sample should be between 98.0 % -101.0 w/w.
Note :

1.

Determine the Assay by titration as an average of two trials.

2.

The difference between two trials should not be more than 1.0

3.

Average should not be done in case any of the trials fails.

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