1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Aspirin
(Acetylsalicylic acid) from the Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1 Q.C Analysts.
4.0 ACCOUNTABILITY:
4.1 Q.C Manager.
5.0 PROCEDURE:
5.1 Characters:
5.1.1
Appearance:
5.1.1.1 White or almost white powder.
5.1.1.2 Crystalline powder.
5.1.1.3 Colourless.
5.1.2
Solubility:
5.1.2.1 Material and equipment:
5.1.2.1.1
Glassware
(test tubes, spatula).
5.1.2.1.2
Ethanol
(96%).
5.1.2.1.3
Purified
water.
5.1.2.2 Sample:
5.1.2.2.1
Small
quantity.
5.1.2.3 Method:
5.1.2.3.1
Take
2 test tubes and add small quantity of sample for testing solubility according
to B.P specifications.
5.1.2.3.2
Add
purified water in test tube 1 and observe.
5.1.2.3.3
Add
ethanol (96%) in test tube 2 and observe.
5.1.2.4 Observations:
5.1.2.4.1
The
sample in test tube 1 containing with water is slightly soluble.
5.1.2.4.2
The
sample in test tube 2 containing with ethanol (96%) is freely soluble.
5.2 Identification
tests:
5.2.1
5.2.1.1 Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Melting
point apparatus (beaker, stirrer, thermometer, capillary tube, burner, thread).
5.2.1.1.3
Desiccator.
5.2.1.1.4
Dilute
sodium hydroxide.
5.2.1.1.5
Dilute
sulfuric acid.
5.2.1.1.6
Purified
water.
5.2.1.2 Sample:
5.2.1.2.1
0.2g.
5.2.1.3 Method:
5.2.1.3.1
Take
a 50.0ml of beaker and add 0.2g of sample in it.
5.2.1.3.2
Add
4ml of dilute sodium hydroxide solution in it with the help of pipette.
5.2.1.3.3
Boil
it for 3min.
5.2.1.3.4
Cool
it.
5.2.1.3.5
Add
5.0ml of dilute sulfuric acid with the help of pipette.
5.2.1.3.6
A
crystalline ppt formed.
5.2.1.3.7
Filter
it.
5.2.1.3.8
Wash
the ppt with the help of water.
5.2.1.3.9
Dry
at 100-105oC in desiccator.
5.2.1.3.10 And then find out the melting point of the
ppt by using melting point apparatus.
5.2.1.3.11 Melting point determination method:
5.2.1.3.11.1 Firstly set the apparatus.
5.2.1.3.11.2
Fill
100ml beaker with water and place wire gauze on tripod stand, put beaker on it.
5.2.1.3.11.3
Heat
up the capillary tube on burner from center such that it divides into two upon
pulling the capillary tube from both sides in opposite directions.
5.2.1.3.11.4
Introduce
a sufficient quantity into a capillary tube to give a compact column 4mm to 6mm
in height.
5.2.1.3.11.5
Tie
up the capillary tube near the thermometer bulb with the help of thread.
5.2.1.3.11.6
And
hang the thermometer on stand such that the capillary tube is not fully
immersed in water. The immersion mark of which is at the level of the surface
of the liquid.
5.2.1.3.11.7
Allow
the burner to heat up the liquid in beaker.
5.2.1.3.11.8
Observe
it closely.
5.2.1.3.11.9
Record
the temperature at which the last particle passes into the liquid phase.
5.2.1.4 Observations:
5.2.1.4.1
The
melting point is 156oC-161oC.
5.2.2
5.2.2.1 Material and equipment:
5.2.2.1.1
Glassware
(according to requirement).
5.2.2.1.2
Calcium
hydroxide.
5.2.2.1.3
Nitrobenzaldehyde
solution.
5.2.2.1.4
Dilute
hydrochloric acid.
5.2.2.1.5
Filter
paper.
5.2.2.1.6
Purified
water.
5.2.2.2 Sample:
5.2.2.2.1
0.1g.
5.2.2.3 Method:
5.2.2.3.1
Take
a test tube and mix 0.1g of substance to be examined with 0.5g of calcium
hydroxide.
5.2.2.3.2
Heat
the mixture on water bath.
5.2.2.3.3
Expose
it to the fumes produced a piece of filter paper impregnated with 0.05ml of
nitrobenzyaldehyde solution.
5.2.2.3.4
Observe
the changes.
5.2.2.3.5
Take
a filter paper and moisten with the dilute hydrochloric acid.
5.2.2.3.6
Observe
the changes.
5.2.2.4 Observations:
5.2.2.4.1
A
greenish-blue or greenish-yellow colour develops on the filter paper
impregnated with nitrobenzyaldehyde.
5.2.2.4.2
The
moisten filter paper with dilute hydrochloric acid colour become blue.
5.2.3
Salicylates test:
5.2.3.1 Material and equipment:
5.2.3.1.1
Glassware
(according to requirement).
5.2.3.1.2
0.5ml
of ferric chloride.
5.2.3.1.3
0.1ml
of acetic acid.
5.2.3.1.4
Purified
water.
5.2.3.2 Sample:
5.2.3.2.1
20.0mg.
5.2.3.3 Method of analysis:
5.2.3.3.1
Take
a test tube and take in it 20.0mg of the ppt obtained in identification test
5.2.1.
5.2.3.3.2
Add
10.0ml of water in it and dissolve it upon heating.
5.2.3.3.3
Cool
it.
5.2.3.3.4
And
then take 1.0ml of the above solution in another test tube for identification
of salicylates.
5.2.3.3.5
Add
0.5ml of ferric chloride solution.
5.2.3.3.6
Observe
the colour change.
5.2.3.3.7
And
after that add 0.1ml of acetic acid.
5.2.3.3.8
Observe
again.
5.2.3.4 Observations:
5.2.3.4.1
A
violet colour is produced upon addition of ferric chloride.
5.2.3.4.2
That
violet colour persists after the addition of acetic acid.
5.3 Assay:
5.3.1
Apparatus:
5.3.1.1 Glassware (according to requirement).
5.3.1.2 Titration apparatus.
5.3.1.3 Water-bath.
5.3.2
Material and reagents:
5.3.2.1 Alcohol.
5.3.2.2 0.5M alcoholic potassium hydroxide.
5.3.2.3 Dilute nitric acid.
5.3.2.4 0.1M silver nitrate.
5.3.2.5 Ferric ammonium sulphate solution.
5.3.2.6 0.1M ammonium thiocyanate.
5.3.2.7 Purified water.
5.3.3
Sample:
5.3.3.1 0.2g.
5.3.4
Method of analysis:
5.3.4.1 Sample titration:
5.3.4.1.1
Take
a ground-glass stoppered flask and take in it 1.0g of sample.
5.3.4.1.2
Dissolve
it in 10.0ml of ethanol (96%).
5.3.4.1.3
Add
50.0ml of 0.5M sodium hydroxide.
5.3.4.1.4
Close
the flask and allow it to stand for 1h.
5.3.4.1.5
Set
titration apparatus.
5.3.4.1.6
Use
0.2ml of phenolphthalein solution as indicator.
5.3.4.1.7
Titrate
with 0.5M hydrochloric acid.
5.3.4.1.8
Note
down the volume used as shown in Annexure-1.
5.3.4.1.9
And
take average.
5.3.4.2 Blank titration:
5.3.4.2.1
Take
a ground-glass stoppered flask and add 10.0ml of ethanol (96%).
5.3.4.2.2
And
add 50.0ml of 0.5M sodium hydroxide and dissolve it.
5.3.4.2.3
Close
the flask and allow it to stand for 1h.
5.3.4.2.4
Set
titration apparatus.
5.3.4.2.5
Use
0.2ml of phenolphthalein solution as indicator.
5.3.4.2.6
Titrate
with 0.5M hydrochloric acid.
5.3.4.2.7
Note
down the volume used as shown in Annexure-1.
5.3.4.2.8
And
take average.
5.3.4.3 Calculate percentage purity.
5.3.4.4 Calculations:
5.3.4.4.1
After
taking average volume of both blank titration and sample titration. Calculate
the volume used by the examined substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.3.4.4.2
For
percentage purity use formula:
%age
purity = volume used by substance x factor x 100
Weight of
sample
5.3.4.4.3
Put
values and calculate %age purity.
5.3.5
Factor:
5.3.5.1 1ml of 0.5M Sodium hydroxide is equivalent
to 45.04mg of C9H8O4.
5.3.6
Limit:
5.3.6.1 99.5% to 101.0% (dried substance).
6.0 REVISION
LOG:
Revision No.
|
Effective Date
|
Reason
|
00
|
New
SOP
|
7.0 REFERENCES:
7.1 The British Pharmacopoeia. Vol I., Official Monograph /Aspirin: 2015, pp. 204-205.
8.0 ANNEXURES:
Annexure 1: Observations
and calculations.
Annexure:
1
Observations
and calculations
Indicator:
___________________
Weight
of sample: ____________
Factor: ____45.04mg.__
Titrant:
_____________________
Sample titration
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
1.
|
|||
2.
|
|||
3.
|
Average volume: _________________
Blank titration
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
1.
|
|||
2.
|
|||
3.
|
Average volume: _________________
Calculations:
Volume used by substance
= Blank titration - Sample titration.
%age purity = volume
used by substance x factor x 100
Weight of sample
Result: ____________________________________________________________________
9.0 ABBREVIATIONS:
Abbreviation
|
Expanded Form
|
SOP
|
Standard
operating procedure
|
&
|
And
|
No.
|
Number
|
Ltd.
|
Limited
|
Sr.#
|
Serial
number
|
Q.C
|
Quality
control
|
%
|
Percentage
|
B.P
|
British
pharmacopoeia
|
g
|
Grams
|
ml
|
Milliliter
|
Min
|
Minutes
|
ppt
|
Precipitates
|
oC
|
Degree
centigrade
|
mm
|
Millimeter
|
mg
|
Milligram
|
M
|
Molar
|
h
|
Hour
|
Vol
|
Volume
|
vi
|
Initial
volume
|
vf
|
Final
volume
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|