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