VALSARTAN METHOD OF ANALYSIS SOP


1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of Valsartan 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  Hygroscopic 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        Anhydrous ethanol.
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, anhydrous ethanol and methylene chloride 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 purified water is practically insoluble.
5.1.2.4.2        The sample in test tube 2 containing with anhydrous ethanol is freely soluble.
5.1.2.4.3        The sample in test tube 3 containing with methylene chloride is sparingly soluble.
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        0.200g of sample.
5.2.1.3  Method:
5.2.1.3.1        Test solution:
5.2.1.3.1.1  Take a beaker of 50.0ml and dissolve 0.200g of sample in sufficient quantity of methanol (approximately 10.0-15.0ml).
5.2.1.3.1.2  Dilute it to 20.0ml with the same solvent.
5.2.1.3.2        Firstly clean the Polarimeter with clean dry cloth, according to SOP.
5.2.1.3.3        Operate the Polarimeter according to SOP.
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        -69.0 to -64.0.
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  70.0ml of 2-propanol.
5.3.2.2  3g/L solution of thymol blue in menthol as an indicator.
5.3.2.3  0.1M tetrabutylammonium hydroxide.
5.3.3        Sample:
5.3.3.1  0.170g of sample.
5.3.4        Method of analysis:
5.3.4.1  Take a 100.0ml of beaker and dissolve 0.170g of sample in 70.0ml of 2-propanol.
5.3.4.2  Fill the right hand side burette with titrant 0.1M tetrabutylammonium hydroxide.
5.3.4.3  Carry out a Potentiometric titration using 3g/L solution of thymol blue in menthol as an indicator.
5.3.4.4  Perform all operations under nitrogen.
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-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 tetrabutylammonium hydroxide in 2-propanol is equivalent to 21.78mg of Valsartan C24H29N5O3.
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 II., Official Monograph /Valsartan: 2015, pp. 1144-1145.
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
v/s
Verses
%
Percentage
mV
Millivolts
oC
Degree centigrade
ml
Milliliter
nm
Nanometer
o
Degree (angle)
l
Length
g
Grams
c
Concentration (g/ml)
g/ml
Gram per milliliter
α
Alpha
λ
Lambda
T
Temperature
Sr.#
Serial number
g/L
Grams per liter
B.P
British pharmacopoeia
Vol
Volume


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