LAMOTRIGINE
SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Lamotrigine
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.
5.1.2.2
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 and anhydrous ethanol in test tube 2 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 very slightly soluble.
5.1.2.4.2
The sample in test
tube 2 containing with anhydrous ethanol is 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
2.0g.
5.2.3
Method:
5.2.3.1
Weigh 2.0g 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 at a pressure not exceeding 0.7kPa for
at least 3 hours.
5.2.3.5
And wait till the
sample loses its moisture.
5.2.3.6
After 3 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
60.0ml of
anhydrous acetic acid.
5.3.2.2
0.1M Perchloric
acid.
5.3.2.3
Crystal violet
solution.
5.3.3
Sample:
5.3.3.1
0.200g.
5.3.4
Method
of analysis:
5.3.4.1 Take
a 100.0ml of beaker and take 0.200g of sample in it.
5.3.4.2 Add
60.0ml of anhydrous acetic acid. Dissolve it by using magnetic stirrer operate
according to SOP.
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 25.61mg of Lamotrigine C9H7Cl2N5.
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
|
7.0 REFERENCES:
7.1
The British
Pharmacopoeia. Vol II.,
Official Monograph /Lamotrigine: 2015, pp. 75-76.
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: ____________________________________________________________
|
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
|