RANITIDINE HYDROCHLORIDE METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of the Ranitidine hydrochloride from
the Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1
Q.C Analysts.
4.0 ACCOUNTABILITY:
4.1
Q.C Manager.
5.0 PROCEDURE:
5.1 Characters:
5.1.1
Appearance:
5.1.1.1
White or pale
yellow.
5.1.1.2
Crystalline
powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (3 test
tubes, 1 spatula).
5.1.2.1.2
Anhydrous ethanol.
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
Purified water.
5.1.2.2
Sample:
5.1.2.2.1
Small quantity.
5.1.2.3
Method:
5.1.2.3.1
Take 3 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 anhydrous
ethanol 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 water is freely soluble.
5.1.2.4.2
The sample in test
tube 2 containing with anhydrous ethanol is sparingly soluble or slightly soluble.
5.1.2.4.3
The sample in test
tube 3 containing with methylene chloride is very slightly soluble.
5.2 Identification
tests:
5.2.1
Chlorides
test:
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Dilute nitric
acid.
5.2.1.1.3
Purified water
(q.s).
5.2.1.1.4
0.4ml of Silver
nitrate R1.
5.2.1.1.5
1.5ml of ammonia.
5.2.1.2
Sample:
5.2.1.2.1
Quantity of
substance to be examined equivalent to about 2.0mg of chloride.
5.2.1.3
Method:
5.2.1.3.1
Take a test tube
add in it 2.0ml of water with the help of pipette.
5.2.1.3.2
Dissolve in 2.0ml
of water a quantity of the substance to be equivalent to about 2.0mg of
chloride.
5.2.1.3.3
Acidify with
dilute nitric acid.
5.2.1.3.4
And add 0.4ml of
silver nitrate R1.
5.2.1.3.5
Shake and allow it
to stand.
5.2.1.3.6
A curdled, white
ppt is formed.
5.2.1.3.7
Centrifuge it in
centrifugation machine, according to SOP No. BM/QCEO/SOP010-00.
5.2.1.3.8
The obtained ppt
is wash with 3 quantities, each of 1ml, of water.
5.2.1.3.9
Carry out this operation
rapidly is subdued light, degrading the fact that the supernatant solution may
not become perfectly clear.
5.2.1.3.10 Suspend
the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.2.1.4
Observations:
5.2.1.4.1
The precipitate
dissolves easily with the possible exception of a few large particles which
dissolves slowly.
5.3 Other
tests:
5.3.1
Solution
S:
5.3.1.1
Material and equipment:
5.3.1.1.1
Glassware (1
beaker, 1 stirrer, 1 spatula).
5.3.1.1.2
Carbon
dioxide-free water.
5.3.1.2
Sample:
5.3.1.2.1
1.0g.
5.3.1.3
Preparation of Solution S:
5.3.1.3.1
Take a beaker of 100.0ml
add 1.0g of sample in it.
5.3.1.3.2
Dissolve it in sufficient
carbon dioxide-free water and dilute to 100ml with the same solvent.
5.3.2
pH:
5.3.2.1
Material and equipment:
5.3.2.1.1
Glassware
(according to the requirement).
5.3.2.1.2
pH meter.
5.3.2.2
Sample:
5.3.2.2.1
Solution S.
5.3.2.3
Method:
5.3.2.3.1
Firstly clean the
pH meter with clean dry cloth, according to SOP.
5.3.2.3.2
Operate the pH
meter according to SOP for operation of pH meter i.e. SOP.
5.3.2.3.3
Rejuvenate the
electrode before use according to SOP instructions, if there is any need of.
5.3.2.3.4
Calibrate the
electrode of the pH meter according to SOP.
5.3.2.3.5
Perform the test
on solution S.
5.3.2.3.6
Take a beaker of
100.0ml and add solution S in it. Such that it immersed electrodes in it
completely.
5.3.2.3.7
Maintain the
temperature of sample at 25oC±2oC.
5.3.2.3.8
Dip the electrode
along with temperature sensor into the sample.
5.3.2.3.9
When dipping
electrode into sample, it must be completely immersed in it.
5.3.2.3.10 Stir
the probe gently in the sample to create a homogeneous sample.
5.3.2.3.11 Allow
the reading to stabilize for a time.
5.3.2.3.12 Record
the observed values of pH & temperature in the respective Annexure-1.
5.3.2.3.13 Wash
the electrodes again after use and store the electrode in storage solution as
recommended in SOP of cleaning, i.e. SOP. Calibrate the instrument before use according to SOP.
5.3.2.4
Observation:
5.3.2.4.1
4.5 to 6.0 for
solution S.
5.3.3
Loss
on drying:
5.3.3.1
Material and equipment:
5.3.3.1.1
Glassware
(according to requirement).
5.3.3.1.2
Vacuum desiccator.
5.3.3.1.3
Diphosphorous
pentaoxide.
5.3.3.1.4
Analytical weighing
balance.
5.3.3.1.5
Spatula.
5.3.3.2
Sample:
5.3.3.2.1
1.0g.
5.3.3.3
Method:
5.3.3.3.1
Weigh 1.0g of the
test sample.
5.3.3.3.2
Set the desiccator
apparatus with desiccant.
5.3.3.3.3
Operate the desiccator
according to the SOP.
5.3.3.3.4
Place the sample
into the china dish or petri dish.
5.3.3.3.5
Set the
temperature 60oC and at under high vacuum, pressure not exceeding
0.1kPa for at least 45 minutes.
5.3.3.3.6
And wait till the
sample loses its moisture.
5.3.3.3.7
After 45 minutes
weigh the sample again by using analytical weighing balance i.e. the final
weight.
5.3.3.3.8
Note down readings
on given Annexure-2.
5.3.3.4
Observations:
5.3.3.4.1
Maximum 0.75%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Analytical
weighing balance.
5.4.1.3
Potentiometer.
5.4.2
Material
and reagents:
5.4.2.1
0.1M sodium
hydroxide.
5.4.2.2
Thymolphthalein
solution.
5.4.2.3
35.0ml of purified
water.
5.4.3
Sample:
5.4.3.1
0.280g.
5.4.4
Method
of analysis:
5.4.4.1 Take
a 50.0ml of beaker and take 0.280g of sample in it.
5.4.4.2 Add
35.0ml of purified water in it and dissolve properly.
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 an indicator.
5.4.4.5 Operate
potentiometer according to SOP.
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-3.
5.4.4.7 Plot
a graph, volume used v/s millivolts.
5.4.4.8 Find
out the END POINT.
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-3.
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 35.09mg of Ranitidine hydrochloride C13H23ClN4O3S.
5.4.6
Limit:
5.4.6.1
98.5% to 101.5%
(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 / Ranitidine hydrochloride: 2015, pp. 730-732.
8.0 ANNEXURES:
Annexure 1: Observations
of pH meter.
Annexure 2: Observations
of percentage loss of drying.
Annexure 3: Assay
observations and calculations (Potentiometric titration)
Annexure:
1
Observations
of pH meter.
|
pH measurement
Result:
_________________________________________________________________
|
Annexure:
2
Observations
of percentage loss of drying
|
Percentage
loss of drying
Apparatus:
____________________
Temperature:
__________________
Weight
of Sample = _____________
Time
period = _____________
Pressure=
_________________
Average % Loss of Moisture: _____________
Remarks:
____________________________________________________________
|
||||||||||||||||||||||||
Annexure:
3
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
|
|
Ltd.
|
Limited
|
|
Sr.#
|
Serial
number
|
|
Q.C
|
Quality
control
|
|
%
|
Percentage
|
|
q.s
|
Quantity
sufficient
|
|
R1
|
Reagent
1
|
|
kPa
|
Kilopascal
|
|
B.P
|
British
pharmacopoeia
|
|
g/L
|
Grams
per liter
|
|
mg
|
Milligram
|
|
Min
|
Minutes
|
|
ml
|
Milligram
|
|
oC
|
Degree
centigrade
|
|
g
|
Grams
|
|
M
|
Molar
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
mV
|
Millivolts
|
|
Ti
|
Initial
temperature
|
|
Tf
|
Final
temperature
|
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