PHENYLEPHRINE HYDROCHLORIDE SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Phenylephrine 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 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 (2 test
tubes, 1 spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
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 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.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1and 2 containing with purified water and Ethanol (96%) is freely soluble.
5.2 Solution
S:
5.2.1
Material and equipment:
5.2.1.1
Glassware (1
50.0ml of beaker, 1 spatula, 1 glass rod, 1 pipette).
5.2.1.2
Analytical
weighing balance.
5.2.1.3
Magnetic stirrer.
5.2.1.4
Carbon-dioxide
free water.
5.2.1.5
Distilled water.
5.2.2
Sample:
5.2.2.1
2.0g.
5.2.3
Preparation of solution
S:
5.2.3.1
Take a beaker of
100.0ml and add sample 2.0g in it.
5.2.3.2
Add in it
sufficient quantity of carbon-dioxide free water prepared from distilled water.
5.2.3.3
Dilute it to
100.0ml with the same solvent.
5.3 Identification
tests:
5.3.1
Specific
optical rotation:
5.3.1.1
Material and equipment:
5.3.1.1.1
Polarimeter.
5.3.1.1.2
Magnetic stirrer.
5.3.1.1.3
Glassware (1
beaker of 50.0ml, 1 stirrer, 1 spatula).
5.3.1.1.4
Purified water.
5.3.1.2
Sample:
5.3.1.2.1
Solution S.
5.3.1.3
Method:
5.3.1.3.1
Take a beaker of
50.0ml and add Solution S in it.
5.3.1.3.2
Firstly clean the
Polarimeter with clean dry cloth, according to SOP.
5.3.1.3.3
Operate the
Polarimeter according to SOP.
5.3.1.3.4
Fill the
Polarimeter tube with blank solution and determine the observed optical
rotation.
5.3.1.3.5
Similarly, fill
the Polarimeter tube with sample solution and determine the observed optical
rotation.
5.3.1.3.6
Note down the
values in annexure-1.
5.3.1.3.7
Calculate the
specific optical rotation by using formula:
[α]λ T = α/lc
5.3.1.4
Observations:
5.3.1.4.1
-43 to -47 (dried
substance).
5.3.2
Melting
point determination:
5.3.2.1
Material and equipment:
5.3.2.1.1
Glassware
(according to requirement).
5.3.2.1.2
Melting point
apparatus.
5.3.2.1.3
Capillary tubes.
5.3.2.1.4
1.0ml of dilute
ammonia R1.
5.3.2.1.5
Ice-water.
5.3.2.1.6
Purified water.
5.3.2.2
Sample:
5.3.2.2.1
0.3g.
5.3.2.3
Method:
5.3.2.3.1
Take a test tube
and add in it 0.3g of sample in it.
5.3.2.3.2
Dissolve the
sample in 3.0ml of purified water and 1.0ml of dilute ammonia R1.
5.3.2.3.3
Initiate
crystallization by scratching the wall of the tube with a glass rod.
5.3.2.3.4
Wash the crystals
with iced water and dry at 105oC for 2h.
5.3.2.3.5
Introduce the
sufficient quantity of sample into a capillary tube.
5.3.2.3.6
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.
5.3.2.3.7
Switch on the
melting point apparatus.
5.3.2.3.8
Operate the
melting point apparatus according to the SOP No. BM/QCEO/SOP009-00.
5.3.2.3.9
Raise the
temperature of the apparatus.
5.3.2.3.10 Record
the temperature at which the last particle passes into the liquid phase.
5.3.2.3.11 Record
measurements in annexure-2.
5.3.2.4
Observations:
5.3.2.4.1
The melting point
is 171oC-176oC.
5.3.3
5.3.3.1
Material and equipment:
5.3.3.1.1
Glassware (1 test
tube, 1 pipette).
5.3.3.1.2
Analytical
weighing balance.
5.3.3.1.3
1.0ml of a 200g/L
solution of sodium hydroxide.
5.3.3.1.4
1.0ml of ether.
5.3.3.1.5
0.05ml of a 125g/L
solution of copper sulfate.
5.3.3.1.6
1.0ml of purified
water.
5.3.3.2
Sample:
5.3.3.2.1
10.0mg.
5.3.3.3
Method:
5.3.3.3.1
Take 1.0ml of
purified water in a test tube and about 10.0mg of sample in it, dissolve it.
5.3.3.3.2
Add 0.05ml of a
125g/L solution of copper sulfate and 1.0ml of a 200g/L solution of sodium
hydroxide.
5.3.3.3.3
Observe the
changes.
5.3.3.3.4
A violet colour is
produced.
5.3.3.3.5
Add 1.0ml of ether
and shake; observe the changes in upper layer.
5.3.3.4
Observations:
5.3.3.4.1
The upper layer
remains colourless.
5.3.4
Chlorides
test:
5.3.4.1
Material and equipment:
5.3.4.1.1
Glassware
(according to requirement).
5.3.4.1.2
Centrifuge
machine.
5.3.4.1.3
Dilute nitric
acid.
5.3.4.1.4
Purified water
(q.s).
5.3.4.1.5
0.4ml of Silver
nitrate R1.
5.3.4.1.6
1.5ml of ammonia.
5.3.4.2
Sample:
5.3.4.2.1
Quantity of
substance to be examined equivalent to about 2.0mg of chloride.
5.3.4.3
Method:
5.3.4.3.1
Take a test tube
add in it 2.0ml of water with the help of pipette.
5.3.4.3.2
Dissolve in 2.0ml
of water a quantity of the substance to be equivalent to about 2.0mg of
chloride.
5.3.4.3.3
Acidify with
dilute nitric acid.
5.3.4.3.4
And add 0.4ml of
silver nitrate R1.
5.3.4.3.5
Shake and allow it
to stand.
5.3.4.3.6
A curdled, white
ppt is formed.
5.3.4.3.7
Centrifuge it in
centrifugation machine, according to SOP.
5.3.4.3.8
The obtained ppt
is wash with 3 quantities, each of 1ml, of water.
5.3.4.3.9
Carry out this
operation rapidly is subdued light, degrading the fact that the supernatant
solution may not become perfectly clear.
5.3.4.3.10 Suspend
the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.3.4.4
Observations:
5.3.4.4.1
The precipitate
dissolves easily with the possible exception of a few large particles which
dissolves slowly.
5.4 Loss
on drying:
5.4.1
Material and equipment:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Analytical
weighing balance.
5.4.1.3
Oven.
5.4.2
Sample:
5.4.2.1
1.0g.
5.4.3
Method:
5.4.3.1
Weigh 1.0g of the
test sample.
5.4.3.2
Set the oven
apparatus. Operate it according to the SOP.
5.4.3.3
Place the sample
into the tray and dry it.
5.4.3.4
Set the
temperature of oven at 105oC for at least 45 minutes.
5.4.3.5
And wait till the
sample loses its moisture.
5.4.3.6
After 45 minutes
weigh the sample again by using analytical weighing balance i.e. the final
weight.
5.4.3.7
Note down readings
on given Annexure-3.
5.4.4
Observation:
5.4.4.1
Maximum 1.0%.
5.5 Assay:
5.5.1
Apparatus:
5.5.1.1
Glassware
(according to requirement).
5.5.1.2
Potentiometer.
5.5.1.3
Magnetic stirrer.
5.5.2
Material
and reagents:
5.5.2.1
5.0ml of 0.1M
hydrochloric acid.
5.5.2.2
80.0ml of ethanol
(96%).
5.5.2.3
0.1M Ethanolic sodium
hydroxide.
5.5.2.4
Thymolphthalein
solution (as indicator).
5.5.3
Sample:
5.5.3.1
0.150g.
5.5.4
Method
of analysis:
5.5.4.1 Take
a 100.0ml of beaker and take 0.150g of sample in it.
5.5.4.2 Add
a mixture of 5.0ml of 0.1M hydrochloric acid and 80.0ml of ethanol (96%), dissolve
by using magnetic stirrer.
5.5.4.3 Fill
the right hand side burette with titrant 0.1M Ethanolic sodium hydroxide.
5.5.4.4 Carry
out a Potentiometric titration using thymolphthalein solution (as indicator).
5.5.4.5 Operate
potentiometer according to SOP.
5.5.4.6 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.
5.5.4.7 Plot
a graph, volume used v/s millivolts.
5.5.4.8 Find
out the END POINT. Read the volume added between the 2 points of inflexion.
5.5.4.9 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.5.4.10 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-4.
5.5.4.11 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.5.4.12 Calculate
percentage purity of the sample by using formula:
%age
purity = volume used by substance x factor x 100
Weight
of sample
5.5.5
Factor:
5.5.5.1 1ml
of 0.1M Ethanolic sodium hydroxide is equivalent to 20.37mg of Phenylephrine hydrochloride C9H14ClNO2.
5.5.6
Limit:
5.5.6.1 98.5%
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 / Phenylephrine
hydrochloride: 2015, pp. 558-560.
7.2
The British
Pharmacopoeia. Vol V., Official
Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0 ANNEXURES:
Annexure 1: Specific
optical rotation observations and calculations.
Annexure 2: Observations
of Melting point apparatus.
Annexure 3: Observations
of Percentage Loss of drying by using oven.
Annexure 4: Assay
observations and calculations (Potentiometric titration).
Annexure: 1
Specific
optical rotation observations and calculations
Specific
optical rotation
Instrument:
___________________
Date:
_______________
Model:
_______________________ Length
of Polarimeter tube: ________________
Sample:
________________________________g.
Solvent:
________________________________ml.
Concentration
of sample solution: ____________g/ml.
Blank solution:
Average: _______________
Optical
rotation of blank solution: _______________
Sample solution:
Average: _______________
Optical
rotation of sample solution: ______________
Optical rotation of substance = Blank solution - Sample
solution.
Specific
optical rotation of sample solution by using formula:
[α]λ T = α/lc
Result: ________________
Remarks:
___________________________________________________________
|
Annexure:
2
Observations
of Melting point apparatus
Sample
= _____________
Time
period = _____________
Sr.#
|
Initial (Ti)
(oC)
|
Final (Tf)
(oC)
|
Tf - Ti
(oC)
|
Average:
_____________
Result: _________________
Remarks:
_______________________________________________________________
Annexure: 3
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:
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
|
Ti
|
Initial
temperature
|
Tf
|
Final
temperature
|
Temp.
|
Temperature
|
v/s
|
Verses
|
Mv
|
Millivolts
|
G
|
Grams
|
ml
|
Milliliter
|
Min
|
Minutes
|
oC
|
Degree
centigrade
|
mg
|
Milligram
|
M
|
Molar
|
%
|
Percentage
|
R
|
Reagent
|
o
|
Degree
(angle)
|
L
|
Length
|
c
|
Concentration
(g/ml)
|
g/ml
|
Gram
per milliliter
|
α
|
Alpha
|
λ
|
Lambda
|