PHOLCODINE METHOD OF ANALYSIS SOP


PHOLCODINE  METHOD OF ANALYSIS SOP


1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Pholcodine 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 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 (4 test tubes, 1 spatula, 1 pipette).
5.1.2.1.2        Ethanol (96%).
5.1.2.1.3        Acetone.
5.1.2.1.4        Dilute mineral acid (e.g. H2SO4).
5.1.2.1.5        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 4 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 acetone in test tube 2 and observe.
5.1.2.3.4        Add ethanol (96%) in test tube 3 and observe.
5.1.2.3.5        Add dilute mineral acid in test tube 4 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 and 3 containing with acetone and ethanol (96%) is freely soluble respectively.
5.1.2.4.3        The sample in test tube 4 containing with dilute mineral acid is dissolved.
5.2  Other tests:
5.2.1        Specific optical rotation:
5.2.1.1  Material and equipment:
5.2.1.1.1        Polarimeter.
5.2.1.1.2        Magnetic stirrer.
5.2.1.1.3        Glassware (1 beaker of 50.0ml, 1 stirrer, 1 spatula).
5.2.1.1.4        Ethanol (96%).
5.2.1.2  Sample:
5.2.1.2.1        1.0g.
5.2.1.3  Method:
5.2.1.3.1        Take a beaker of 50.0ml and add 1.0g of sample in it.
5.2.1.3.2        Dissolve it in sufficient quantity of ethanol (96%) by using magnetic stirrer.
5.2.1.3.3        And finally dilute it to 50.0ml with the same solvent.
5.2.1.3.4        Firstly clean the Polarimeter with clean dry cloth, according to SOP
5.2.1.3.5        Operate the Polarimeter according to SOP
5.2.1.3.6        Fill the Polarimeter tube with blank solution and determine the observed optical rotation.
5.2.1.3.7        Similarly, fill the Polarimeter tube with sample solution and determine the observed optical rotation.
5.2.1.3.8        Note down the values in annexure-1.
5.2.1.3.9        Calculate the specific optical rotation by using formula:
                                                      [α]λ T = α/lc
5.2.1.4  Observations:
5.2.1.4.1        -98 to -94 (dried substance).
5.2.2        Loss on drying:
5.2.2.1  Material and equipment:
5.2.2.1.1        Glassware (according to requirement).
5.2.2.1.2        Analytical weighing balance.
5.2.2.1.3        Oven.
5.2.2.2  Sample:
5.2.2.2.1        0.5g.
5.2.2.3  Method:
5.2.2.3.1        Weigh 1.0g of the test sample.
5.2.2.3.2        Set the oven apparatus. Operate it according to the SOP.
5.2.2.3.3        Place the sample into the tray and dry it.
5.2.2.3.4        Set the temperature of oven at 105oC for at least 45 minutes.
5.2.2.3.5        And wait till the sample loses its moisture.
5.2.2.3.6        After 45 minutes weigh the sample again by using analytical weighing balance i.e. the final weight.
5.2.2.3.7        Note down readings on given Annexure-2.
5.2.2.4  Observation:
5.2.2.4.1        3.9% to 4.5%.
5.3  Assay:
5.3.1        Apparatus:
5.3.1.1  Glassware (according to requirement).
5.3.1.2  Potentiometer.
5.3.1.3  Magnetic stirrer.
5.3.2        Material and reagents:
5.3.2.1  50.0ml of anhydrous acetic acid.
5.3.2.2  0.1M Perchloric acid.
5.3.2.3  Crystal violet solution.
5.3.3        Sample:
5.3.3.1  0.180g.
5.3.4        Method of analysis:
5.3.4.1  Take a 50.0ml of beaker and take 0.180g of sample in it.
5.3.4.2  Add 50.0ml of anhydrous acetic acid in it and dissolve by using magnetic stirrer i.e. SOP.
5.3.4.3  Fill the right hand side burette with titrant 0.1M Perchloric acid.
5.3.4.4  Carry out a Potentiometric titration using crystal violet solution as an indicator.
5.3.4.5  Operate potentiometer according to SOP.
5.3.4.6  To neutralize analyte add titrant fixed volume (1ml, 0.5ml or 0.1ml) from burette every time note the reading of change in potential difference (millivolts) for each addition in given annexure-3.
5.3.4.7  Plot a graph, volume used v/s millivolts.
5.3.4.8  Find out the END POINT.
5.3.4.9  Peak of graph indicates END POINT i.e. the point at which maximum millivolts. Note down volume used at that point.
5.3.4.10    Perform blank titration without using sample. Similarly, as sample titration performed. Record observations in annexure-3.
5.3.4.11    Calculate volume used by substance by using formula:
Volume used by substance = Blank titration - Sample titration.
5.3.4.12    Calculate percentage purity of the sample by using formula:
%age purity = volume used by substance x factor x 100
                         Weight of sample
5.3.5        Factor:
5.3.5.1  1ml of 0.1M Perchloric acid is equivalent to 19.93mg of Pholcodine C23H30N2O4.
5.3.6        Limit:
5.3.6.1  98.5% to 101.5% (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 / Pholcodine: 2015, pp. 570-571.
8.0  ANNEXURES:
Annexure 1: Specific optical rotation observations and calculations.
Annexure 2: Observations of Percentage Loss of drying by using oven.
Annexure 3: Assay observations and calculations (Potentiometric titration).

Annexure: 1
Specific optical rotation observations and calculations
Specific optical rotation
Instrument: ___________________                                              Date: _______________
Model: _______________________        Length of Polarimeter tube: ________________
Sample: ________________________________g.
Solvent: ________________________________ml.
Concentration of sample solution: ____________g/ml.
Blank solution:
Sr.#
Blank solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of blank solution: _______________
Sample solution:
Sr.#
Sample solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of sample solution: ______________
Optical rotation of substance = Blank solution - Sample solution.



Specific optical rotation of sample solution by using formula:
[α]λ T = α/lc






                                                                      Result: ________________
Remarks: ___________________________________________________________





Annexure: 2
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: 3
Assay observations and calculations (Potentiometric titration)
Potentiometric titration
Reference electrode: ___________________
Indicator electrode: ____________________
Speed of magnetic stirrer: _______________
Titrant used: __________________________
Indicator: ____________________________
Blank titration:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












Plot a graph, volume used v/s millivolts and find out peak of graph i.e. END POINT of blank titration.
Sample titration:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












Plot a graph, volume used v/s millivolts and find out peak of graph i.e. END POINT of sample titration:
Volume used by Blank titration: __________________
Volume used by Sample titration: _________________
Volume used by substance = Blank titration - Sample titration.


mV used by Blank titration: __________________
mV used by Sample titration: _________________
mV used by substance = Blank titration - Sample titration.

Volume used by substance: _______________________
Voltmeter (mV) used by substance: _________________


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
Ti
Initial temperature
Tf
Final temperature
Temp.
Temperature
v/s
Verses
mV
Millivolts
g
Grams
ml
Milliliter
Min
Minutes
oC
Degree centigrade
mg
Milligram
M
Molar
%
Percentage
R
Reagent
o
Degree (angle)
l
Length
c
Concentration (g/ml)
g/ml
Gram per milliliter
α
Alpha
λ
Lambda


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