ETHAMBUTOL HYDROCHLORIDE SOP


1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of the Ethambutol 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 almost white.
5.1.1.2  Crystalline powder.
5.1.1.3  Hygroscopic.
5.1.2        Solubility:
5.1.2.1  Material and equipment:
5.1.2.1.1        Glassware (2 test tubes, 1 spatula, 1 pipette).
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 1 containing with water is freely soluble.
5.1.2.4.2        The sample in test tube 2 containing with ethanol (96%) is soluble.
5.2  Identification tests:
5.2.1         
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (according to requirement).
5.2.1.1.2        0.2ml of copper sulfate solution R.
5.2.1.1.3        10.0ml of Purified water.
5.2.1.1.4        0.5ml of dilute sodium hydroxide solution R.
5.2.1.2  Sample:
5.2.1.2.1        0.1g.
5.2.1.3  Method:
5.2.1.3.1        Take a test tube add in it 0.1g of the sample in it.
5.2.1.3.2        Add 10.0ml of Purified water R. dissolve it thoroughly.
5.2.1.3.3        Add 0.2ml of copper sulfate solution R and 0.5ml of dilute sodium hydroxide solution R.
5.2.1.3.4        Observe the changes.
5.2.1.4  Observations:
5.2.1.4.1        A blue colour is produced.
5.2.2        Chlorides test:
5.2.2.1  Material and equipment:
5.2.2.1.1        Glassware (according to requirement).
5.2.2.1.2        Centrifugation machine.
5.2.2.1.3        Dilute nitric acid.
5.2.2.1.4        Purified water.
5.2.2.1.5        0.4ml of Silver nitrate R1.
5.2.2.1.6        Ammonia.
5.2.2.2  Sample:
5.2.2.2.1        Quantity of substance to be examined equivalent to about 2.0mg of chloride.
5.2.2.3  Method:
5.2.2.3.1        Take a test tube add in it 2.0ml of water with the help of pipette.
5.2.2.3.2        Dissolve in 2.0ml of water a quantity of the substance to be equivalent to about 2.0mg of chloride.
5.2.2.3.3        Acidify with dilute nitric acid.
5.2.2.3.4        And add 0.4ml of silver nitrate R1.
5.2.2.3.5        Shake and allow it to stand.
5.2.2.3.6        A curdled, white ppt is formed.
5.2.2.3.7        Centrifuge it in centrifugation machine, according to SOP No. BM/QCEO/SOP010-00.
5.2.2.3.8        The obtained ppt is wash with 3 quantities, each of 1ml, of water.
5.2.2.3.9        Carry out this operation rapidly is subdued light, degrading the fact that the supernatant solution may not become perfectly clear.
5.2.2.3.10    Suspend the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.2.2.4  Observations:
5.2.2.4.1        The precipitate dissolves easily with the possible exception of a few large particles which dissolves slowly.
5.3  Loss on drying:
5.3.1        Material and equipment:
5.3.1.1  Glassware (according to requirement).
5.3.1.2  Analytical weighing balance.
5.3.1.3  Oven.
5.3.2        Sample:
5.3.2.1  0.5g.
5.3.3        Method:
5.3.3.1  Weigh 0.5g of the test sample.
5.3.3.2  Set the oven apparatus. Operate it according to the SOP.
5.3.3.3  Place the sample into the tray and dry it.
5.3.3.4  Set the temperature of oven at 105oC for at least 3hours.
5.3.3.5  And wait till the sample loses its moisture.
5.3.3.6  After 3 hours weigh the sample again by using analytical weighing balance i.e. the final weight.
5.3.3.7  Note down readings on given Annexure-1.
5.3.4        Observation:
5.3.4.1  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  1.0ml of 0.1M hydrochloric acid.
5.4.2.2  0.1M sodium hydroxide.
5.4.2.3  Thymolphthalein solution as an indicator.
5.4.2.4  50.0ml of Purified water.
5.4.3        Sample:
5.4.3.1  0.200g.
5.4.4        Method of analysis:
5.4.4.1  Take a 50.0ml of beaker and 0.200g of sample in it.
5.4.4.2  Add 50.0ml of purified water and add 1.0ml of 0.1M hydrochloric acid in it and dissolve by using magnetic stirrer operate according to SOP.
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-2.
5.4.4.7  Plot a graph, volume used v/s millivolts.
5.4.4.8  Find out the END POINT. Read the volume added between the 2 points of inflexion.
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-2.
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 27.72mg of ethambutol hydrochloride C10H26Cl2N2O2.
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 I., Official Monograph / Ethambutol Hydrochloride: 2015, pp. 895-896.
7.2  The British Pharmacopoeia. Vol V., Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0  ANNEXURES:
Annexure 1: Observations of Percentage Loss of drying by using oven.
Annexure 2: Assay observations and calculations (Potentiometric titration).







Annexure: 1
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: 2
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
Q.C
Quality control
%
Percentage
B.P
British pharmacopoeia
mg
Milligram
ml
Milliliter
ppt
Precipitate
g
Grams
M
Molar
Vol
Volume
QCA
Quality control active ingredient
F
Format
v/s
Verses
mV
Millivolts
oC
Degree centigrade
R
Reagent


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