RISPERIDONE METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Risperidone
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 (4 test
tubes, spatula).
5.1.2.1.2
Purified water.
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
Ethanol (96%).
5.1.2.1.5
Dilute acid
solution (e.g. dilute HNO3).
5.1.2.2
Sample:
5.1.2.2.1
Small quantity.
5.1.2.3
Method:
5.1.2.3.1
Take 4 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, Methylene chloride in test tube 2, ethanol (96%) in test tube
3, dilute acid solution like HNO3 in test tube 4 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 Methylene chloride is freely soluble.
5.1.2.4.3
The sample in test
tube 3 containing with ethanol (96%) is sparingly soluble.
5.1.2.4.4
The sample in test
tube 4 containing with dilute acid solution like HNO3 is dissolved.
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 4 hours.
5.2.3.5
And wait till the
sample loses its moisture.
5.2.3.6
After 4 hours
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
Apparatus:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Potentiometer.
5.3.2
Material
and reagents:
5.3.2.1
1 volume of
anhydrous acetic acid.
5.3.2.2
7 volumes of methyl
ethyl ketone.
5.3.2.3
0.1M Perchloric
acid.
5.3.2.4
Crystal violet
solution.
5.3.3
Sample:
5.3.3.1
0.160g.
5.3.4
Method
of analysis:
5.3.4.1 Take
a 100.0ml of beaker and take 0.160g of sample in it.
5.3.4.2 Add
70.0ml of a mixture of 1 volume of anhydrous acetic acid and 7 volumes of
methyl ethyl ketone. Dissolve it by using magnetic stirrer i.e..
5.3.4.3 Fill
the right hand side burette with titrant 0.1M Perchloric acid.
5.3.4.4 Carry
out a Potentiometric titration using crystal violet solution as an indicator.
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-2.
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-2.
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 Perchloric acid is equivalent to 20.53mg of Risperidone C23H27FN4O2.
5.3.6
Limit:
5.3.6.1
99.0% to 101.0%
(dried substance).
6.0 REVISION LOG:
|
Revision No.
|
Effective Date
|
Reason
|
|
00
|
|
New SOP
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7.0 REFERENCES:
7.1
The British
Pharmacopoeia. Vol II.,
Official Monograph /Risperidone: 2015, pp. 756-758.
8.0 ANNEXURES:
Annexure 1: Observations
of Percentage Loss of drying by using oven.
Annexure 2: Assay
observations and calculations (Potentiometric titration).
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)
|
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: ____________________________________________________________
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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
|
|
h
|
Hours
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
mV
|
Millivolts
|
|
v/s
|
Verses
|
|
kPa
|
Kilo
Pascal
|
|
Min
|
Minutes
|