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:
Sr.#
Blank solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of blank solution: _______________
Sample solution:
Sr.#
Sample solution
Temperature
Optical rotation
(α)












                                                                                                 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= _________________
Sr.#
Time (min)
Weight of sample (g)
% Loss of Moisture
Initial weight
Final weight















Average % Loss of Moisture: _____________

% 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:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












Plot a graph, volume used v/s millivolts and find out peak of graph i.e. END POINT of blank titration.
Sample titration:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












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


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