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
Sr.#
Temperature
pH

















Result: _________________________________________________________________
















Annexure: 2
Observations of percentage loss of drying
Percentage loss of drying
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: 3
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
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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