PROMETHAZINE HYDROCHLORIDE METHOD OF ANALYSIS SOP


1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Promethazine 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 faintly yellowish.
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.
5.1.2.1.4        Methylene chloride.
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.
5.1.2.3.4        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 purified water is very soluble.
5.1.2.4.2        The sample in test tube 2 and 3 containing with Ethanol (96%) and Methylene chloride is freely soluble, respectively.
5.2  Identification tests:
5.2.1         
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (1 test tube, 1 pipette, 1 spatula).
5.2.1.1.2        Analytical weighing balance.
5.2.1.1.3        Water bath.
5.2.1.1.4        1.0ml of nitric acid
5.2.1.1.5        Purified water.
5.2.1.2  Sample:
5.2.1.2.1        0.1g.
5.2.1.3  Method:
5.2.1.3.1        Take 3.0ml of purified water in test tube and add 0.1g of sample, dissolve it.
5.2.1.3.2        Add drop-wise 1.0ml of nitric acid.
5.2.1.3.3        The precipitate is formed which rapidly dissolves to give a red solution, becoming orange and then yellow
5.2.1.3.4        Heat to boiling on burner.
5.2.1.3.5        Observe changes again.
5.2.1.4  Observations:
5.2.1.4.1        The solution becomes orange and an orange-red ppt is formed.
5.2.2        Chlorides test:
5.2.2.1  Material and equipment:
5.2.2.1.1        Glassware (1 test tube, 1 spatula, 1 pipette).
5.2.2.1.2        0.2g of potassium dichromate.
5.2.2.1.3        1.0ml of sulfuric acid.
5.2.2.1.4        0.1ml of diphenylcarbazide solution.
5.2.2.1.5        Filter paper.
5.2.2.2  Sample:
5.2.2.2.1        Quantity of substance to be examined equivalent to about 15.0mg of chloride.
5.2.2.3  Method:
5.2.2.3.1        Take a test tube add in it a quantity of the substance to be equivalent to about 15.0mg of chloride.
5.2.2.3.2        Add 0.2g of potassium dichromate and 1.0ml of sulfuric acid.
5.2.2.3.3        Take a filter paper strip impregnated with 0.1ml of diphenylcarbazide solution.
5.2.2.3.4        Place it over the opening of the test tube.
5.2.2.3.5        Observe the changes.
5.2.2.3.6        And impregnated paper must not come into contact with the potassium dichromate.
5.2.2.4  Observations:
5.2.2.4.1        The paper turns violet-red.
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  1.0g.
5.3.3        Method:
5.3.3.1  Weigh 1.0g 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 45 minutes.
5.3.3.5  And wait till the sample loses its moisture.
5.3.3.6  After 45 minutes 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  5.0ml of 0.01M hydrochloric acid.
5.4.2.2  50.0ml of ethanol (96%).
5.4.2.3  0.1M sodium hydroxide.
5.4.2.4  Thymolphthalein solution (as indicator).
5.4.3        Sample:
5.4.3.1  0.250g.
5.4.4        Method of analysis:
5.4.4.1  Take a 100.0ml of beaker and take 0.250g of sample in it.
5.4.4.2  Add a mixture of 5.0ml of 0.01M hydrochloric acid and 50.0ml of ethanol (96%) dissolve by using magnetic stirrer i.e. SOP No. BM/QCEO/SOP007-00.
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 indicator).
5.4.4.5  Operate potentiometer according to SOP No. BM/QCEO/SOP036-00.
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 32.09mg of Promethazine hydrochloride C17H21ClN2S.
5.4.6        Limit:
5.4.6.1  99.0% to 101.0% (anhydrous 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 / Promethazine hydrochloride: 2015, pp. 675-676.
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
QCA
Quality control active ingredient
F
Format
Q.C
Quality control
Vol
Volume
v/s
Verses
mV
Millivolts
g
Grams
ml
Milliliter
Min
Minutes
oC
Degree centigrade
mg
Milligram
M
Molar
%
Percentage
R
Reagent


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