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:
Thickness of cell:

Maxima absorption wavelength:
249nm.
Sample:

Other reagent used:


No. of obs.
Concentration
(c)
Wavelength
(╬╗)
Absorbance
(a)
Specific absorbance
A (1%,1cm)











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= _________________
Sr.#
Time (min)
Weight of sample (g)
% Loss of Moisture
Initial weight
Final weight















Average % Loss of Moisture: _____________

% 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
╬╗
Lambda
UV/VIS
Ultraviolet/ visible
nm
Nanometer
h
Hour
A
Absorbance
g/L
Grams per liter
vi
Initial volume
vf
Final volume


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