PHENIRAMINE MALEATE SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Pheniramine 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.
5.1.1.2
Crystalline
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
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 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 Ethanol (96%)
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 Methylene
chloride 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 soluble.
5.1.2.4.2
The sample in test
tube 2, 3 & 4 containing with ethanol (96%), methanol and methylene chloride
is freely soluble respectively.
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 106oC-109oC.
5.2.2
UV/VIS
absorption Spectrophotometry:
5.2.2.1
Material and equipment:
5.2.2.1.1
UV/VIS
Spectrophotometer.
5.2.2.1.2
Glassware
(according to requirement).
5.2.2.1.3
0.1M hydrochloric
acid.
5.2.2.2
Sample:
5.2.2.2.1
40.0mg.
5.2.2.3
Method:
5.2.2.3.1
Test
solution:
5.2.2.3.1.1 Take
a beaker of 100.0ml and add 40.0mg of sample in it.
5.2.2.3.1.2 Dissolve
it in sufficient quantity of 0.1M hydrochloric acid.
5.2.2.3.1.3 And
dilute it to 100.0ml with the same acid.
5.2.2.3.1.4 Take
5.0ml of this solution in 50.0ml of beaker.
5.2.2.3.1.5 And
dilute it to 50.0ml with 0.1M hydrochloric acid.
5.2.2.3.2
Spectral
range:
5.2.2.3.2.1 220-320nm.
5.2.2.3.3
Absorption
maximum:
5.2.2.3.3.1 At
265nm.
5.2.2.3.4
Shoulder:
5.2.2.3.4.1 At
261nm.
5.2.2.3.5
Operate the UV/VIS
spectrophotometer according to the SOP No. BM/QCEO/SOP027-00.
5.2.2.3.6
Measure the
absorbance of the resulting solution at the maximum wavelength 265nm.
5.2.2.3.7
Note down values
of absorbance in annexure-2.
5.2.2.3.8
Calculate the
specific absorbances at the absorption maximum by using formula:
1cmA1% = __a__
b.c
5.2.2.4
Observations:
5.2.2.4.1
Specific
absorbance at absorption maximum:
5.2.2.4.1.1 200
to 220.
5.3 Loss
on drying:
5.3.1.1
Material and equipment:
5.3.1.1.1
Glassware
(according to requirement).
5.3.1.1.2
Desiccator.
5.3.1.1.3
Diphosphorous
pentaoxide.
5.3.1.1.4
Analytical weighing
balance.
5.3.1.1.5
Spatula.
5.3.1.2
Sample:
5.3.1.2.1
1.0g.
5.3.1.3
Method:
5.3.1.3.1
Weigh 1g of the
test sample.
5.3.1.3.2
Set the desiccator
apparatus with desiccant.
5.3.1.3.3
Operate the desiccator
according to the SOP.
5.3.1.3.4
Place the sample
into the china dish or petri dish.
5.3.1.3.5
Set the
temperature 60oC and at 1.5kPa to 2.5kPa pressure for at least 3h.
5.3.1.3.6
And wait till the
sample loses its moisture.
5.3.1.3.7
After 3h weigh the
sample again by using analytical weighing balance i.e. the final weight.
5.3.1.3.8
Note down readings
on given Annexure-3.
5.3.1.4
Observations:
5.3.1.4.1
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
50.0ml of
anhydrous acetic acid.
5.4.2.2
0.1M Perchloric
acid.
5.4.2.3
Crystal violet
solution.
5.4.3
Sample:
5.4.3.1
0.13g.
5.4.4
Method
of analysis:
5.4.4.1 Take
a 50.0ml of beaker and take 0.13g of sample in it.
5.4.4.2 Add
50.0ml of anhydrous acetic acid in it and dissolve by using magnetic stirrer.
5.4.4.3 Fill
the right hand side burette with titrant 0.1M Perchloric acid.
5.4.4.4 Carry
out a Potentiometric titration using crystal violet 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-4.
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-4.
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 Perchloric acid is equivalent to 17.82mg of Pheniramine maleate C20H24N2O4.
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 II.,
Official Monograph /Pheniramine maleate: 2015, pp. 540-541.
8.0 ANNEXURES:
Annexure 1: Observations
of Melting point apparatus.
Annexure 2: Observations
of UV/VIS spectrophotometer.
Annexure 3: Observations
of percentage loss of drying.
Annexure 4: Assay
observations and calculations (Potentiometric titration).
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
and Calculations of UV/VIS spectrophotometer
|
UV/VIS spectrophotometer
Model:
_____________________________ Date: _________________
OBSERVATIONS:
CALCULATIONS:
1cmA1%
= __a__
b.c
Results:
_______________
Remarks:
______________________________________________________________
|
Annexure: 3
Observations
of percentage loss of drying
|
Percentage
loss of drying
Apparatus:
____________________
Temperature:
__________________
Pressure:
_____________________
Weight
of Sample = _____________
Time
period = _____________
Average % Loss of Moisture: _____________
Remarks:
____________________________________________________________
|
||||||||||||||||||||||||
Annexure:
4
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
|
|
mg
|
Milligram
|
|
ml
|
Milliliter
|
|
ppt
|
Precipitate
|
|
M
|
Molar
|
|
g
|
Grams
|
|
Cm
|
Centimeter
|
|
Min
|
Minute
|
|
%
|
Percentage
|
|
Ti
|
Initial
temperature
|
|
Tf
|
Final
temperature
|
|
Temp.
|
Temperature
|
|
v/s
|
Verses
|
|
mV
|
Millivolts
|
|
oC
|
Degree
centigrade
|
|
R
|
Reagent
|
|
λ
|
Lambda
|
|
UV/VIS
|
Ultraviolet/
visible
|
|
nm
|
Nanometer
|
|
h
|
Hours
|
|
A
|
Absorbance
|
|
BP
|
British
Pharmacopoeia
|