PARACETAMOL METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Paracetamol from the Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1
Q.C Analyst.
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.
5.1.1.2
Crystalline
powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (3 test
tubes, 1 spatula, 1 pipette).
5.1.2.1.2
Alcohol.
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
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 3 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 alcohol in
test tube 2 and observe.
5.1.2.3.4
Add Methylene
chloride in test tube 3 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 containing with purified water is sparingly soluble.
5.1.2.4.2
The sample in test
tube 2 containing with alcohol is freely soluble.
5.1.2.4.3
The sample in test
tube 3 containing with Methylene chloride is very slightly soluble.
5.2 Identification
tests:
5.2.1
Melting
point determination:
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Melting point
apparatus.
5.2.1.1.3
Capillary tubes.
5.2.1.1.4
Purified water.
5.2.1.2
Sample:
5.2.1.2.1
Sufficient
quantity of sample.
5.2.1.3
Method:
5.2.1.3.1
Introduce the
sufficient quantity of sample into a capillary tube.
5.2.1.3.2
Set the apparatus
and immerse the capillary tube into the apparatus such that the closed end is
near the centre of the bulb of thermometer.
5.2.1.3.3
Switch on the
melting point apparatus.
5.2.1.3.4
Operate the
melting point apparatus according to the SOP
5.2.1.3.5
Raise the
temperature of the apparatus.
5.2.1.3.6
Record the
temperature at which the last particle passes into the liquid phase.
5.2.1.3.7
Record
measurements in annexure-1.
5.2.1.4
Observations:
5.2.1.4.1
The melting point
is 168oC-172oC.
5.2.2
UV/VIS
absorption Spectrophotometry:
5.2.2.1
Material and equipment:
5.2.2.1.1
UV/VIS
Spectrophotometer.
5.2.2.1.2
Glassware
(according to requirement).
5.2.2.1.3
Methanol.
5.2.2.1.4
0.5ml of a 10.3g/L
solution of hydrochloric acid.
5.2.2.2
Sample:
5.2.2.2.1
0.1g.
5.2.2.3
Method:
5.2.2.3.1
Test
solution:
5.2.2.3.1.1 Take
a beaker of 100.0ml and add 0.1g of sample in it.
5.2.2.3.1.2 Dissolve
it in sufficient quantity of methanol.
5.2.2.3.1.3 And
dilute it to 100.0ml with the same solvent.
5.2.2.3.1.4 Take
1.0ml of this solution in 100.0ml of beaker.
5.2.2.3.1.5 And
add 0.5ml of a 10.3g/L solution of hydrochloric acid.
5.2.2.3.1.6 And
dilute it to 100.0ml with methanol.
5.2.2.3.1.7 Protect
the solution from bright light and immediately measure the absorbance.
5.2.2.3.2
Absorption
maxima:
5.2.2.3.2.1 Absorption
maxima at 249nm.
5.2.2.3.3
Operate the UV/VIS
spectrophotometer according to the SOP.
5.2.2.3.4
Measure the
absorbance of the resulting solution at absorption maxima 249nm
5.2.2.3.5
Note down values
of absorbance in annexure-2.
5.2.2.3.6
Calculate the specific
absorbances at the absorption maxima by using formula:
1cmA1% = __a__
b.c
5.2.2.4
Observations:
5.2.2.4.1
Specific
absorbance at maximum 249nm:
5.2.2.4.1.1 860
to 980.
5.2.3
Acetyl
determination test:
5.2.3.1
Material and equipment:
5.2.3.1.1
Glassware (2 test
tubes, 1 pipette, 1 spatula).
5.2.3.1.2
Analytical
weighing balance.
5.2.3.1.3
Water-bath.
5.2.3.1.4
Ice-bath.
5.2.3.1.5
1.0ml of
hydrochloric acid.
5.2.3.1.6
0.05ml of a 4.9g/L
solution of potassium dichromate.
5.2.3.1.7
Purified water.
5.2.3.2
Sample:
5.2.3.2.1
0.1g.
5.2.3.3
Method:
5.2.3.3.1
Take a test tube
and add 0.1g of sample in it.
5.2.3.3.2
Add 1.0ml of
hydrochloric acid, heat it on burner till boiling for 3min.
5.2.3.3.3
Add 1.0ml of
purified water and cool it on ice-bath.
5.2.3.3.4
Observe the
changes.
5.2.3.3.5
No ppt is formed.
5.2.3.3.6
Add 0.05ml of a
4.9g/L solution of potassium dichromate.
5.2.3.3.7
Observe the
changes again.
5.2.3.4
Observations:
5.2.3.4.1
A violet colour
develops which does not change to red.
5.3 Loss
on drying:
5.3.1
Material and equipment:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Analytical
weighing balance.
5.3.1.3
Oven.
5.3.2
Sample:
5.3.2.1
1.0g.
5.3.3
Method:
5.3.3.1
Weigh 1.0g of the test
sample.
5.3.3.2
Set the oven
apparatus. Operate it according to the SOP
5.3.3.3
Place the sample
into the tray and dry it.
5.3.3.4
Set the
temperature of oven at 105oC for 45min.
5.3.3.5
And wait till the
sample loses its moisture.
5.3.3.6
After 45min weigh
the sample again by using analytical weighing balance i.e. the final weight.
5.3.3.7
Note down readings
on given Annexure-3.
5.3.4
Observation:
5.3.4.1
Maximum 0.5%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Titration
apparatus.
5.4.1.3
Reflux-condenser
apparatus.
5.4.2
Material
and reagents:
5.4.2.1
30.0ml of dilute
sulfuric acid.
5.4.2.2
40.0g of ice.
5.4.2.3
15.0ml of dilute
hydrochloric acid.
5.4.2.4
0.1ml of ferroin.
5.4.2.5
0.1M of cerium
sulfate.
5.4.2.6
Purified water.
5.4.3
Sample:
5.4.3.1
0.3g.
5.4.4
Method
of analysis:
5.4.4.1 Sample
titration:
5.4.4.1.1
Take a beaker of
100.0ml and add 0.3g of sample in it.
5.4.4.1.2
Add a mixture of 10.0ml
of purified water and 30.0ml of dilute sulfuric acid.
5.4.4.1.3
Set the reflux
condenser apparatus.
5.4.4.1.4
Boil under a
reflux condenser for 1h.
5.4.4.1.5
Cool it and dilute
it to 100.0ml with purified water.
5.4.4.1.6
Take 20.0ml of the
solution add 40.0ml of purified water, 40.0g of ice, 15.0ml of dilute
hydrochloric acid.
5.4.4.1.7
Use 0.1ml of
ferroin as indicator.
5.4.4.1.8
Take a titration
flask and add sample solution approximate 10.0ml.
5.4.4.1.9
Set titration
apparatus.
5.4.4.1.10 Titrate
with 0.1M of cerium sulfate, until a greenish-yellow colour is obtained.
5.4.4.1.11 Note
down the volume used as shown in Annexure-4.
5.4.4.1.12 Take
at least 3 readings and take average of it.
5.4.4.2 Blank
titration:
5.4.4.2.1
Take a beaker of
100.0ml and add a mixture of 10.0ml of purified water and 30.0ml of dilute
sulfuric acid.
5.4.4.2.2
Set the reflux
condenser apparatus.
5.4.4.2.3
Boil under a
reflux condenser for 1h.
5.4.4.2.4
Cool it and dilute
it to 100.0ml with purified water.
5.4.4.2.5
Take 20.0ml of the
solution add 40.0ml of purified water, 40.0g of ice, 15.0ml of dilute hydrochloric
acid.
5.4.4.2.6
Use 0.1ml of
ferroin as indicator.
5.4.4.2.7
Take a titration
flask and add sample solution approximate 10.0ml.
5.4.4.2.8
Set titration
apparatus.
5.4.4.2.9
Titrate with 0.1M
of cerium sulfate, until a greenish-yellow colour is obtained.
5.4.4.2.10 Note
down the volume used as shown in Annexure-4.
5.4.4.2.11 Take
at least 3 readings and take average of it.
5.4.4.3 Calculate
percentage purity.
5.4.4.4 Calculations:
5.4.4.4.1
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.
5.4.4.4.2
For percentage
purity use formula:
%age
purity = volume used by substance x factor x 100
Weight of sample
5.4.4.4.3
Put values and
calculate %age purity.
5.4.5
Factor:
5.4.5.1 1ml
of 0.1M of cerium sulfate is equivalent to 7.56mg of Paracetamol C8H9NO2.
5.4.6
Limit:
5.4.6.1 99.0%
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 II.,
Official Monograph /Paracetamol: 2015, pp. 498-499.
7.2
The British
Pharmacopoeia. Vol V.,
Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0 ANNEXURES:
Annexure 1: Observations
of Melting point apparatus.
Annexure 2: Observations
of UV/VIS spectrophotometer.
Annexure 3: Observations
of Percentage Loss of drying by using oven.
Annexure 4: Observations
and calculations of assay.
Annexure:
1
Observations
of Melting point apparatus
Sample
= _____________
Time
period = _____________
Sr.#
|
Initial (Ti)
(oC)
|
Final (Tf)
(oC)
|
Tf - Ti
(oC)
|
Average:
_____________
Result: _________________
Remarks:
_______________________________________________________________
Annexure: 2
Observations
and Calculations of UV/VIS spectrophotometer
UV/VIS spectrophotometer
Model:
_____________________________ Date:
_________________
OBSERVATIONS:
CALCULATIONS:
1cmA1%
= __a__
b.c
Results:
_______________
Remarks:
______________________________________________________________
|
Annexure: 3
Observations
of percentage loss of drying by using Oven
Percentage
loss of drying by using Oven
Apparatus:
___________________
Temperature:
__________________
Weight
of Sample = _____________
Time
period = _____________
Pressure=
_________________
Average % Loss of Moisture: _____________
Remarks:
_______________________________________________________________
|
||||||||||||||||||||||||
Annexure:
4
Observations
and calculations of assay
Indicator:
___________________
Weight
of sample: ____________
Factor:
______________
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
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|
Q.C
|
Quality
control
|
Vol
|
Volume
|
mg
|
Milligram
|
ml
|
Milliliter
|
ppt
|
Precipitate
|
M
|
Molar
|
g
|
Grams
|
Min
|
Minute
|
%
|
Percentage
|
Ti
|
Initial
temperature
|
Tf
|
Final
temperature
|
Temp.
|
Temperature
|
oC
|
Degree
centigrade
|
R
|
Reagent
|
λ
|
Lambda
|
UV/VIS
|
Ultraviolet/
visible
|
nm
|
Nanometer
|
h
|
Hour
|
A
|
Absorbance
|
g/L
|
Grams
per liter
|
vi
|
Initial
volume
|
vf
|
Final
volume
|