CIMETIDINE HYDROCHLORIDE SOP


CIMETIDINE HYDROCHLORIDE SOP



1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Cimetidine 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        Anhydrous ethanol.
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 anhydrous ethanol in test tube 2 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.
5.2  Identification tests:
5.2.1        UV/VIS absorption Spectrophotometry:
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (according to requirement).
5.2.1.1.2        UV/VIS Spectrophotometer.
5.2.1.1.3        0.2M sulfuric acid.
5.2.1.2  Sample:
5.2.1.2.1        70.0mg.
5.2.1.3  Absorption maxima:
5.2.1.3.1        At 218nm.
5.2.1.4  Test solution:
5.2.1.4.1        Take a beaker of 100.0ml and add in it 70.0mg of the sample.
5.2.1.4.2        Dissolve it in sufficient quantity of 0.2M sulfuric acid.
5.2.1.4.3        And dilute it to 100.0ml with the same acid.
5.2.1.4.4        Take 2.0ml of this solution in another beaker.
5.2.1.4.5        And dilute it to 100.0ml with 0.2M sulfuric acid.
5.2.1.5  Method:
5.2.1.5.1        Switch ON the UV/VIS spectrophotometer.
5.2.1.5.2        Observe the test solution on absorption maxima i.e. 218nm.
5.2.1.5.3        Note down the absorbance in annexure-1.
5.2.1.5.4        Calculate the specific absorbance by using formula:
5.2.1.5.5        Mm
5.2.1.6  Observations:
5.2.1.6.1        Specific absorbance at the absorption maximum at 218nm is 650 to 705.
5.3  Identification tests:
5.3.1        Chlorides test:
5.3.1.1  Material and equipment:
5.3.1.1.1        Glassware (according to requirement).
5.3.1.1.2        Dilute nitric acid.
5.3.1.1.3        Purified water (q.s).
5.3.1.1.4        0.4ml of Silver nitrate R1.
5.3.1.1.5        1.5ml of ammonia.
5.3.1.2  Sample:
5.3.1.2.1        Quantity of substance to be examined equivalent to about 2.0mg of chloride.
5.3.1.3  Method:
5.3.1.3.1        Take a test tube add in it 2.0ml of water with the help of pipette.
5.3.1.3.2        Dissolve in 2.0ml of water a quantity of the substance to be equivalent to about 2.0mg of chloride.
5.3.1.3.3        Acidify with dilute nitric acid.
5.3.1.3.4        And add 0.4ml of silver nitrate R1.
5.3.1.3.5        Shake and allow it to stand.
5.3.1.3.6        A curdled, white ppt is formed.
5.3.1.3.7        Centrifuge it in centrifugation machine, according
5.3.1.3.8        The obtained ppt is wash with 3 quantities, each of 1ml, of water.
5.3.1.3.9        Carry out this operation rapidly is subdued light, degrading the fact that the supernatant solution may not become perfectly clear.
5.3.1.3.10    Suspend the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.3.1.4  Observations:
5.3.1.4.1        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.
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-2.
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 0.01M hydrochloric acid.
5.5.2.2  50.0ml of ethanol (96%).
5.5.2.3  0.1M sodium hydroxide.
5.5.2.4  Thymolphthalein solution (as indicator).
5.5.3        Sample:
5.5.3.1  0.2g.
5.5.4        Method of analysis:
5.5.4.1  Take a 100.0ml of beaker and take 0.2g of sample in it.
5.5.4.2  Dissolve it in a mixture of 5.0ml of 0.01M hydrochloric acid and 50.0ml of ethanol (96%) by using magnetic stirrer.
5.5.4.3  Fill the right hand side burette with titrant 0.1M sodium hydroxide.
5.5.4.4  Carry out a Potentiometric titration using thymolphthalein solution (as indicator).
5.5.4.5  Operate potentiometer.
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-3.
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-3.
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 sodium hydroxide is equivalent to 28.88mg of cimetidine hydrochloride C10H17ClN6S.
5.5.6        Limit:
5.5.6.1  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 I., Official Monograph / Cimetidine Hydrochloride: 2015, pp. 554-556.
7.2  The British Pharmacopoeia. Vol V., Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0  ANNEXURES:
Annexure 1: Calculations of UV/VIS spectrophotometer.
Annexure 2: Observations of Percentage Loss of drying by using oven.
Annexure 3: Assay observations and calculations (Potentiometric titration).


Annexure: 1
Calculations of UV/VIS spectrophotometer
UV/VIS spectrophotometer
Model: _____________________________                             Date: _________________
OBSERVATIONS:
Thickness of cell:

Spectral range:

Maxima absorption wavelength

Sample:

Other reagent used:


No. of obs.
Concentration
Wavelength
Absorbance
Specific absorbance
A (1%,1cm)











CALCULATIONS:
By using formulas:
1.      1cmA1% =  __a__
                             b.c



Results: _______________
Remarks: ______________________________________________________________



Annexure: 2
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: 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
No.
Number  
Ltd.
Limited
QCA
Quality control active ingredient
F
Format
Q.C
Quality control
Vol
Volume
BP
British Pharmacopoeia
v/s
Verses
mV
Millivolts
g
Grams
ml
Milliliter
Min
Minutes
oC
Degree centigrade
mg
Milligram
M
Molar
%
Percentage
R
Reagent
UV/VIS
Ultraviolet/ visible
cm
Centimeter
λ
Lambda


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