DOMPERIDONE MALEATE SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Domperidone Maleate 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, 1 spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Purified water.
5.1.2.1.4
Methanol.
5.1.2.1.5
Dimethylformamide.
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 and observe.
5.1.2.3.3
Add
Dimethylformamide in test tube 2 and observe.
5.1.2.3.4
Add Methanol in
test tube 3 and observe.
5.1.2.3.5
Add Ethanol (96%)
in test tube 4 and observe
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 Dimethylformamide is sparingly soluble.
5.1.2.4.3
The sample in test
tube 3 containing with Methanol is slightly soluble.
5.1.2.4.4
The sample in test
tube 4 containing with ethanol (96%) very slightly soluble.
5.2 Identification
tests:
5.2.1
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware (2 test
tubes, 1 pipette, 1 spatula).
5.2.1.1.2
Analytical
weighing balance.
5.2.1.1.3
Water-bath.
5.2.1.1.4
Vortex mixer.
5.2.1.1.5
Mortar and pestle.
5.2.1.1.6
1.0ml of strong
sodium hydroxide solution.
5.2.1.1.7
Ether.
5.2.1.1.8
Resorcinol.
5.2.1.1.9
Sulfuric acid.
5.2.1.1.10 2.0ml
of bromine water.
5.2.1.1.11 Purified
water.
5.2.1.2
Sample:
5.2.1.2.1
0.1g.
5.2.1.3
Method:
5.2.1.3.1
Take mortar and
pestle and add 0.1g of sample in it and add a mixture of 1.0ml of strong sodium
hydroxide solution and 3.0ml of purified water with the help of pipette, and
triturate it.
5.2.1.3.2
Take sample in
test tube and shake with 3 quantities each of 5.0ml of ether.
5.2.1.3.3
Take 0.1ml of
aqueous layer in another test tube A after separating layers.
5.2.1.3.4
Add a solution of
10.0mg of resorcinol in 3.0ml of sulfuric acid.
5.2.1.3.5
Heat it on water-bath
for 15min, observe change.
5.2.1.3.6
No colour
develops.
5.2.1.3.7
To the rest of the
aqueous layer in another test tube B add 2.0ml of bromine solution.
5.2.1.3.8
Heat on water-bath
for 15min and then heat to boiling and cool it.
5.2.1.3.9
Take 0.1ml of this
solution in another test tube C.
5.2.1.3.10 Add
a solution of 10.0mg of resorcinol in 3.0ml of sulfuric acid.
5.2.1.3.11 Heat
it on water-bath for 15min and observe the changes.
5.2.1.4
Observations:
5.2.1.4.1
A violet colour
develops.
5.3 Loss
on drying:
5.3.1
Material and equipment:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Analytical
weighing balance.
5.3.1.3
Oven.
5.3.2
Sample:
5.3.2.1
1.0g.
5.3.3
Method:
5.3.3.1
Weigh 1.0g of the
test sample.
5.3.3.2
Set the oven
apparatus. Operate it according to the SOP.
5.3.3.3
Place the sample
into the tray and dry it.
5.3.3.4
Set the
temperature of oven at 105oC for 45min.
5.3.3.5
And wait till the
sample loses its moisture.
5.3.3.6
After 45min weigh
the sample again by using analytical weighing balance i.e. the final weight.
5.3.3.7
Note down readings
on given Annexure-1.
5.3.4
Observation:
5.3.4.1
Maximum 0.25%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Titration
apparatus.
5.4.1.3
Water-bath.
5.4.2
Material
and reagents:
5.4.2.1
50.0ml of
anhydrous acetic acid.
5.4.2.2
0.2ml of
naphtholbenzein solution (as indicator).
5.4.2.3
0.1M perchloric
acid.
5.4.3
Sample:
5.4.3.1
0.4g.
5.4.4
Method
of analysis:
5.4.4.1 Sample
titration:
5.4.4.1.1
Take a flask and
add in it 0.4g of sample.
5.4.4.1.2
Dissolve it in 50.0ml
of anhydrous acetic acid.
5.4.4.1.3
Set titration
apparatus.
5.4.4.1.4
Use 0.2ml of
naphtholbenzein solution as indicator.
5.4.4.1.5
Titrate with 0.1M
perchloric acid, until the colour is changes from orange-yellow to green.
5.4.4.1.6
Note down the
volume used as shown in Annexure-2.
5.4.4.1.7
Take at least 3
readings and take average.
5.4.4.2 Blank
titration:
5.4.4.2.1
Take a flask and
add in it 50.0ml of anhydrous acetic acid.
5.4.4.2.2
Set titration
apparatus.
5.4.4.2.3
Use 0.2ml of
naphtholbenzein solution as indicator.
5.4.4.2.4
Titrate with 0.1M
perchloric acid, until the colour is changes from orange-yellow to green.
5.4.4.2.5
Note down the
volume used as shown in Annexure-2.
5.4.4.2.6
Take at least 3
readings and take average.
5.4.4.3 Calculate
percentage purity.
5.4.4.4 Calculations:
5.4.4.4.1
After taking
average volume of both blank titration and sample titration. Calculate the
volume used by the examined substance by using formula:
Volume used by
substance = Blank titration - Sample titration.
5.4.4.4.2
For percentage
purity use formula:
%age purity = volume
used by substance x factor x 100
Weight of sample
5.4.4.4.3
Put values and calculate
%age purity.
5.4.5
Factor:
5.4.5.1 1ml
of 0.1M perchloric acid is equivalent to 54.20mg of Domperidone maleate C26H28ClN5O6.
5.4.6
Limit:
5.4.6.1 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 I., Official Monograph / Domperidone Maleate: 2015, pp. 804-806.
8.0 ANNEXURES:
Annexure 1: Observations
of Percentage Loss of drying by using oven.
Annexure 2: Observations
and calculations of assay.
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
Observations
and calculations assay
Indicator:
___________________
Weight
of sample: ____________
Factor: ______________
Titrant:
_____________________
Sample titration
|
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
|
1.
|
|
|
|
|
2.
|
|
|
|
|
3.
|
|
|
|
Average volume: _________________
Blank titration
|
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
|
1.
|
|
|
|
|
2.
|
|
|
|
|
3.
|
|
|
|
Average volume: _________________
Calculations:
Volume used by substance = Blank
titration - Sample titration.
%age purity = volume used by
substance x factor x 100
Weight of sample
Result:
____________________________________________________________________
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
|
|
Vol
|
Volume
|
|
BP
|
British
Pharmacopoeia
|
|
mg
|
Milligram
|
|
ml
|
Milliliter
|
|
M
|
Molar
|
|
g
|
Grams
|
|
Min
|
Minute
|
|
%
|
Percentage
|
|
R
|
Reagent
|
|
oC
|
Degree
centigrade
|
|
vi
|
Initial
volume
|
|
vf
|
Final
volume
|