DOMPERIDONE
SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Domperidone from the Pharmacopoeia 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 Ethanol (96%)
in test tube 3 and observe.
5.1.2.3.5
Add methanol 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 practically insoluble.
5.1.2.4.2
The sample in test
tube 2 containing with Dimethylformamide is soluble.
5.1.2.4.3
The sample in test
tube 3 & 4 containing with ethanol (96%) and Methanol is slightly soluble.
5.2 Identification
tests:
5.2.1
Melting
point determination:
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Melting point
apparatus.
5.2.1.1.3
Capillary tubes.
5.2.1.1.4
Purified water.
5.2.1.2
Sample:
5.2.1.2.1
Sufficient
quantity of sample.
5.2.1.3
Method:
5.2.1.3.1
Introduce the
sufficient quantity of sample into a capillary tube.
5.2.1.3.2
Set the apparatus
and immerse the capillary tube into the apparatus such that the closed end is
near the centre of the bulb of thermometer.
5.2.1.3.3
Switch on the
melting point apparatus.
5.2.1.3.4
Operate the
melting point apparatus according to the SOP No. BM/QCEO/SOP009-00.
5.2.1.3.5
Raise the
temperature of the apparatus.
5.2.1.3.6
Record the
temperature at which the last particle passes into the liquid phase.
5.2.1.3.7
Record
measurements in annexure-1.
5.2.1.4
Observations:
5.2.1.4.1
The melting point
is 244oC-248oC.
5.2.2
Non-nitrogen
substituted barbiturates:
5.2.2.1
Material and equipment:
5.2.2.1.1
Glassware (2 test
tubes, 1 pipette, 1 spatula).
5.2.2.1.2
Analytical
weighing balance.
5.2.2.1.3
3.0ml of methanol.
5.2.2.1.4
100.0g/L solution
of cobalt nitrate.
5.2.2.1.5
100.0g/L solution
of calcium chloride.
5.2.2.1.6
0.1ml of dilute
sodium hydroxide solution.
5.2.2.2
Sample:
5.2.2.2.1
5.0mg.
5.2.2.3
Method:
5.2.2.3.1
Take a test tube
and dissolve 5.0mg of the substance to be examined in 3.0ml of methanol.
5.2.2.3.2
And then add 0.1ml
of a solution containing 100.0g/L solution of cobalt nitrate and 100.0g/L
solution of calcium chloride.
5.2.2.3.3
Mix it and add,
with shaking 0.1ml of dilute sodium hydroxide solution.
5.2.2.3.4
Observe the
changes.
5.2.2.4
Observations:
5.2.2.4.1
A violet-blue
colour and ppt are formed.
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 No. BM/QCEO/SOP035-00.
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-2.
5.3.4
Observation:
5.3.4.1
Maximum 0.5%.
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
Anhydrous acetic
acid.
5.4.2.2
Methyl ethyl
ketone.
5.4.2.3
0.2ml of
naphtholbenzein solution (as indicator).
5.4.2.4
0.1M perchloric
acid.
5.4.3
Sample:
5.4.3.1
0.3g.
5.4.4
Method
of analysis:
5.4.4.1 Sample
titration:
5.4.4.1.1
Take a flask and
add in it 0.3g of sample.
5.4.4.1.2
Dissolve it in 50.0ml
of a mixture of 1 volume of anhydrous acetic acid and 7 volumes of Methyl ethyl
ketone.
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-3.
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 a mixture of 1 volume of anhydrous acetic acid and 7
volumes of Methyl ethyl ketone.
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-3.
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 42.59mg of Domperidone C22H24ClN5O2.
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: 2015, pp. 802-804.
7.2
The British
Pharmacopoeia. Vol V.,
Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0 ANNEXURES:
Annexure 1: Observations
of Melting point apparatus.
Annexure 2: Observations
of Percentage Loss of drying by using oven.
Annexure 3: Observations
and calculations of assay.
Annexure: 1
Observations
of Melting point apparatus
Sample
= _____________
Time
period = _____________
|
Sr.#
|
Initial (Ti)
(oC)
|
Final (Tf)
(oC)
|
Tf - Ti
(oC)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Average:
_____________
Result: _________________
Remarks:
_______________________________________________________________
Annexure:
2
Observations
of percentage loss of drying
|
Percentage
loss of drying
Weight
of granules (Sample) = _____________
Time
period = _____________
Average % Loss of Moisture: _____________
|
Annexure:
3
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
|
|
Ti
|
Initial
temperature
|
|
Tf
|
Final
temperature
|
|
Temp.
|
Temperature
|