CLOPIDOGREL HYDROGEN SULPHATE B.P SOP


 CLOPIDOGREL HYDROGEN SULPHATE B.P SOP

1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of Clopidogrel hydrogen sulphate 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.
5.1.2        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        Purified water.
5.1.2.1.3        Methanol.
5.1.2.1.4        Cyclohexane.
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, methanol and cyclohexane in each test tube separately in a small volume and observe the solubility of the sample.
5.1.2.4  Observations:
5.1.2.4.1        The sample in test tube 1 containing with water is freely soluble.
5.1.2.4.2        The sample in test tube 2 containing with methanol is freely soluble.
5.1.2.4.3        The sample in test tube 3 containing with cyclohexane is practically insoluble.
5.2  Identification 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        Analytical weighing balance.
5.2.1.1.3        Glassware (1 beaker of 50.0ml, 1 stirrer, 1 spatula).
5.2.1.1.4        Methanol.
5.2.1.2  Sample:
5.2.1.2.1        0.250g of sample.
5.2.1.3  Method:
5.2.1.3.1        Test solution:
5.2.1.3.1.1  Take a beaker of 25.0ml and dissolve 0.250g of sample in sufficient quantity of methanol (approximately 10.0-15.0ml).
5.2.1.3.1.2  Dilute it to 25.0ml with the same solvent.
5.2.1.3.2        Firstly clean the Polarimeter with clean dry cloth,
5.2.1.3.3        Operate the Polarimeter0
5.2.1.3.4        Fill the Polarimeter tube with blank solution and determine the observed optical rotation.
5.2.1.3.5        Similarly, fill the Polarimeter tube with sample solution and determine the observed optical rotation.
5.2.1.3.6        Note down the values in annexure-2.
5.2.1.3.7        Calculate the specific optical rotation by using formula:
[α]λ T = α/lc
5.2.1.4  Observations:
5.2.1.4.1        +54.0 to +58.0.
5.2.2        Sulfates test:
5.2.2.1  Material and equipment:
5.2.2.1.1        Glassware (3 test tubes, 1 pipette).
5.2.2.1.2        Barium chloride.
5.2.2.1.3        Dilute hydrochloric acid.
5.2.2.1.4        Purified water.
5.2.2.2  Sample:
5.2.2.2.1        45.0mg of sample.
5.2.2.3  Method:
5.2.2.3.1        Test solution:
5.2.2.3.1.1  Take a test tube and add purified water in small quantity. (approx. 5.0ml)
5.2.2.3.1.2  Dissolve sample in it completely and perform test on it.
5.2.2.3.2        Add 1.0ml of dilute hydrochloric acid and 1.0ml of barium chloride solution.
5.2.2.3.3        Observe changes.
5.2.2.4  Observations:
5.2.2.4.1        White ppt produced.
5.3  Assay:
5.3.1        Apparatus:
5.3.1.1  Glassware (according to requirement).
5.3.1.2  Potentiometer.
5.3.2        Material and reagents:
5.3.2.1  10.0ml of acetone.
5.3.2.2  10.0ml of methanol.
5.3.2.3  30.0ml of purified water.
5.3.2.4  0.1M sodium hydroxide.
5.3.2.5  Thymolphthalein solution as an indicator.
5.3.3        Sample:
5.3.3.1  0.106g of sample.
5.3.4        Method of analysis:
5.3.4.1  Take a 50.0ml of beaker and prepare a mixture of 10.0ml of acetone, 10.0ml of methanol & 30.0ml of purified water.
5.3.4.2  Take 0.106g of sample and dissolve it in above prepare mixture by using stirrer.
5.3.4.3  Fill the right hand side burette with titrant 0.1M sodium hydroxide
5.3.4.4  Carry out a Potentiometric titration using Thymolphthalein solution as an indicator.
5.3.4.5  Operate potentiometer.
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-1.
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-1.
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 Sodium hydroxide is equivalent to 20.99mg of Clopidogrel hydrogen sulphate C16H18ClNO6S2.
5.3.6        Limit:
5.3.6.1  99.0% to 101.0% (anhydrous 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 /Clopidogrel Hydrogen Sulphate: 2015, pp. 599-601.
8.0  ANNEXURES:
Annexure 1: Assay observations and calculations (Potentiometric titration).
Annexure 2: Specific optical rotation observations and calculations.


Annexure: 1
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: ____________________________________________________________



Annexure: 2
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: ___________________________________________________________






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
mg
Milligrams
M
Molar
g
Grams
ml
Milliliter
v/s
Verses
%
Percentage
Sr.#
Serial number
B.P
British pharmacopoeia
mV
Millivolts
Vol
Volume


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