PROMETHAZINE HYDROCHLORIDE METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Promethazine hydrochloride 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 faintly
yellowish.
5.1.1.2
Crystalline
powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (2 test
tubes, 1 spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Purified water.
5.1.2.1.4
Methylene
chloride.
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 observe.
5.1.2.3.3
Add Ethanol (96%)
in test tube 2 and observe.
5.1.2.3.4
Add Methylene
chloride in test tube 3 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 containing with purified water is very soluble.
5.1.2.4.2
The sample in test
tube 2 and 3 containing with Ethanol (96%) and Methylene chloride is freely
soluble, respectively.
5.2 Identification
tests:
5.2.1
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware (1 test
tube, 1 pipette, 1 spatula).
5.2.1.1.2
Analytical
weighing balance.
5.2.1.1.3
Water bath.
5.2.1.1.4
1.0ml of nitric
acid
5.2.1.1.5
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 3.0ml of
purified water in test tube and add 0.1g of sample, dissolve it.
5.2.1.3.2
Add drop-wise
1.0ml of nitric acid.
5.2.1.3.3
The precipitate is
formed which rapidly dissolves to give a red solution, becoming orange and then
yellow
5.2.1.3.4
Heat to boiling on
burner.
5.2.1.3.5
Observe changes
again.
5.2.1.4
Observations:
5.2.1.4.1
The solution
becomes orange and an orange-red ppt is formed.
5.2.2
Chlorides
test:
5.2.2.1
Material and equipment:
5.2.2.1.1
Glassware (1 test
tube, 1 spatula, 1 pipette).
5.2.2.1.2
0.2g of potassium
dichromate.
5.2.2.1.3
1.0ml of sulfuric
acid.
5.2.2.1.4
0.1ml of
diphenylcarbazide solution.
5.2.2.1.5
Filter paper.
5.2.2.2
Sample:
5.2.2.2.1
Quantity of
substance to be examined equivalent to about 15.0mg of chloride.
5.2.2.3
Method:
5.2.2.3.1
Take a test tube
add in it a quantity of the substance to be equivalent to about 15.0mg of
chloride.
5.2.2.3.2
Add 0.2g of
potassium dichromate and 1.0ml of sulfuric acid.
5.2.2.3.3
Take a filter
paper strip impregnated with 0.1ml of diphenylcarbazide solution.
5.2.2.3.4
Place it over the
opening of the test tube.
5.2.2.3.5
Observe the
changes.
5.2.2.3.6
And impregnated
paper must not come into contact with the potassium dichromate.
5.2.2.4
Observations:
5.2.2.4.1
The paper turns
violet-red.
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 at least 45 minutes.
5.3.3.5
And wait till the
sample loses its moisture.
5.3.3.6
After 45 minutes
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 0.5%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Potentiometer.
5.4.1.3
Magnetic stirrer.
5.4.2
Material
and reagents:
5.4.2.1
5.0ml of 0.01M
hydrochloric acid.
5.4.2.2
50.0ml of ethanol
(96%).
5.4.2.3
0.1M sodium
hydroxide.
5.4.2.4
Thymolphthalein
solution (as indicator).
5.4.3
Sample:
5.4.3.1
0.250g.
5.4.4
Method
of analysis:
5.4.4.1 Take
a 100.0ml of beaker and take 0.250g of sample in it.
5.4.4.2 Add
a mixture of 5.0ml of 0.01M hydrochloric acid and 50.0ml of ethanol (96%) dissolve
by using magnetic stirrer i.e. SOP No. BM/QCEO/SOP007-00.
5.4.4.3 Fill
the right hand side burette with titrant 0.1M sodium hydroxide.
5.4.4.4 Carry
out a Potentiometric titration using thymolphthalein solution (as indicator).
5.4.4.5 Operate
potentiometer according to SOP No. BM/QCEO/SOP036-00.
5.4.4.6 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.
5.4.4.7 Plot
a graph, volume used v/s millivolts.
5.4.4.8 Find
out the END POINT. Read the volume added between the 2 points of inflexion.
5.4.4.9 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.4.4.10 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.4.4.11 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.4.4.12 Calculate
percentage purity of the sample by using formula:
%age
purity = volume used by substance x factor x 100
Weight of sample
5.4.5
Factor:
5.4.5.1 1ml
of 0.1M sodium hydroxide is equivalent to 32.09mg of Promethazine hydrochloride C17H21ClN2S.
5.4.6
Limit:
5.4.6.1 99.0%
to 101.0% (anhydrous 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 / Promethazine hydrochloride: 2015, pp. 675-676.
7.2
The British
Pharmacopoeia. Vol V.,
Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
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
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
Q.C
|
Quality
control
|
|
Vol
|
Volume
|
|
v/s
|
Verses
|
|
mV
|
Millivolts
|
|
g
|
Grams
|
|
ml
|
Milliliter
|
|
Min
|
Minutes
|
|
oC
|
Degree
centigrade
|
|
mg
|
Milligram
|
|
M
|
Molar
|
|
%
|
Percentage
|
|
R
|
Reagent
|