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:
Plot a graph, volume used v/s millivolts and find out peak
of graph i.e. END POINT of blank titration.
Sample
titration:
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:
Average: _______________
Optical
rotation of blank solution: _______________
Sample solution:
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
|