QUETIAPINE FUMERATE METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Quetiapine Fumarate 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 (2 test
tubes, spatula).
5.1.2.1.2
Purified water.
5.1.2.1.3
Anhydrous ethanol.
5.1.2.1.4
Methanol.
5.1.2.2
Sample:
5.1.2.2.1
Small quantity.
5.1.2.3
Method:
5.1.2.3.1
Take 2 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, anhydrous ethanol in test tube 2 and methanol in test tube 3 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, 2 & 3 containing with purified water, anhydrous ethanol and
methanol are slightly soluble.
5.2 Loss
on drying:
5.2.1
Material and equipment:
5.2.1.1
Glassware
(according to requirement).
5.2.1.2
Analytical
weighing balance.
5.2.1.3
Oven.
5.2.2
Sample:
5.2.2.1
1.0g.
5.2.3
Method:
5.2.3.1
Weigh 1.0g of the
test sample.
5.2.3.2
Set the oven
apparatus. Operate it according to the SOP.
5.2.3.3
Place the sample
into the tray and dry it.
5.2.3.4
Set the
temperature of oven at 105oC for at least 45 minutes.
5.2.3.5
And wait till the
sample loses its moisture.
5.2.3.6
After 45 minutes
weigh the sample again by using analytical weighing balance i.e. the final
weight.
5.2.3.7
Note down readings
on given Annexure-1.
5.2.4
Observation:
5.2.4.1
Maximum 0.5%.
5.3 Assay:
5.3.1
Quetiapine
fumarate:
5.3.1.1
Apparatus:
5.3.1.1.1
Glassware
(according to requirement).
5.3.1.1.2
Potentiometer.
5.3.1.2
Material
and reagents:
5.3.1.2.1
40.0ml of
anhydrous acetic acid.
5.3.1.2.2
0.1M Perchloric
acid.
5.3.1.2.3
Crystal violet
solution.
5.3.1.3
Sample:
5.3.1.3.1
0.170g.
5.3.1.4
Method
of analysis:
5.3.1.4.1
Take a 100.0ml of
beaker and take 0.170g of sample in it.
5.3.1.4.2
Add 40.0ml of
anhydrous acetic acid. Dissolve it by using magnetic stirrer i.e. SOP.
5.3.1.4.3
Fill the right
hand side burette with titrant 0.1M Perchloric acid.
5.3.1.4.4
Carry out a
Potentiometric titration using crystal violet solution as an indicator.
5.3.1.4.5
Operate
potentiometer according to SOP.
5.3.1.4.6
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-2.
5.3.1.4.7
Plot a graph,
volume used v/s millivolts.
5.3.1.4.8
Find out the END
POINT.
5.3.1.4.9
Peak of graph
indicates END POINT i.e. the point at which maximum millivolts. Note down
volume used at that point.
5.3.1.4.10 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.3.1.4.11 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.3.1.4.12 Calculate
percentage purity of the sample by using formula:
%age purity = volume used by substance x factor x 100
Weight of
sample
5.3.1.5 Factor:
5.3.1.5.1
1ml of 0.1M Perchloric
acid is equivalent to 22.08mg of Quetiapine fumerate C46H54N6O8S2.
5.3.1.6 Limit:
5.3.1.6.1
99.0% to 101.0%
(dried substance).
5.3.2
Fumaric
acid:
5.3.2.1
Apparatus:
5.3.2.1.1
Glassware
(according to requirement).
5.3.2.1.2
Potentiometer.
5.3.2.2
Material
and reagents:
5.3.2.2.1
Methanol.
5.3.2.2.2
Purified water.
5.3.2.2.3
0.1M sodium
hydroxide.
5.3.2.2.4
Thymolphthalein
solution.
5.3.2.3
Sample:
5.3.2.3.1
0.350g.
5.3.2.4
Method
of analysis:
5.3.2.4.1
Take a 100.0ml of
beaker and take 0.350g of sample in it.
5.3.2.4.2
Add 70.0ml of a
mixture of equal volumes of methanol and purified water. Dissolve it by using
magnetic stirrer i.e. SOP.
5.3.2.4.3
Fill the right
hand side burette with titrant 0.1M sodium hydroxide.
5.3.2.4.4
Carry out a
Potentiometric titration using Thymolphthalein solution as an indicator.
5.3.2.4.5
Operate
potentiometer according to SOP.
5.3.2.4.6
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.
5.3.2.4.7
Plot a graph,
volume used v/s millivolts.
5.3.2.4.8
Find out the END
POINT.
5.3.2.4.9
Peak of graph
indicates END POINT i.e. the point at which maximum millivolts. Note down
volume used at that point.
5.3.2.4.10 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-3.
5.3.2.4.11 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.3.2.4.12 Calculate
percentage purity of the sample by using formula:
%age purity = volume used by substance x factor x 100
Weight of
sample
5.3.2.5 Factor:
5.3.2.5.1
1ml of 0.1M sodium
hydroxide is equivalent to 5.804mg of Fumaric acid C4H4O4.
5.3.2.6 Limit:
5.3.2.6.1
12.5% to 13.8%
(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 /Quetiapine Fumarate: 2015, pp. 709-711.
8.0 ANNEXURES:
Annexure 1: Observations
of Percentage Loss of drying by using oven.
Annexure 2: Assay
observations and calculations (Potentiometric titration) for Quetiapine fumarate.
Annexure 3: Assay
observations and calculations (Potentiometric titration) for Fumaric acid.
Annexure:
1
Observations
of percentage loss of drying by using Oven
|
Percentage
loss of drying by using Oven
Apparatus:
____________________
Temperature:
__________________
Weight
of Sample = _____________
Time
period = _____________
Pressure=
_________________
Average % Loss of Moisture: _____________
Remarks: _______________________________________________________________
|
||||||||||||||||||||||||
Annexure:
2
Assay
observations and calculations (Potentiometric titration) for Quetiapine
fumarate
|
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:
3
Assay
observations and calculations (Potentiometric titration) for Fumaric acid
|
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: ____________________________________________________________
|
9.0 ABBREVIATIONS:
|
Abbreviation
|
Expanded Form
|
|
SOP
|
Standard
operating procedure
|
|
&
|
And
|
|
No.
|
Number
|
|
Ltd.
|
Limited
|
|
Q.C
|
Quality
control
|
|
B.P
|
British
pharmacopoeia
|
|
M
|
Molar
|
|
g
|
Grams
|
|
ml
|
Milliliter
|
|
mg
|
Milligram
|
|
%
|
Percentage
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
mV
|
Millivolts
|
|
v/s
|
Verses
|
|
Min
|
Minutes
|