DIPHENHYDRAMINE HYDROCHLORIDE SOP


DIPHENHYDRAMINE HYDROCHLORIDE SOP

1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Diphenhydramine 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, 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        Alcohol (e.g. 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 Alcohol in test tube 2 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 containing with Ethanol (96%) is freely soluble.
5.2  Identification tests:
5.2.1        Melting point determination:
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (according to requirement).
5.2.1.1.2        Melting point apparatus.
5.2.1.1.3        Capillary tubes.
5.2.1.1.4        Burner.
5.2.1.1.5        Desiccator.
5.2.1.1.6        Purified water.
5.2.1.2  Sample:
5.2.1.2.1        Sufficient quantity of sample.
5.2.1.3  Method:
5.2.1.3.1        Unless otherwise prescribed, dry the finely powdered substance in vacuo and over the anhydrous silica gel for 24 hrs.
5.2.1.3.2        Introduce the sufficient quantity of sample into a capillary tube.
5.2.1.3.3        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.
5.2.1.3.4        Switch on the melting point apparatus.
5.2.1.3.5        Operate the melting point apparatus according to the SOP.
5.2.1.3.6        Raise the temperature of the apparatus.
5.2.1.3.7        Record the temperature at which the last particle passes into the liquid phase.
5.2.1.3.8        Record measurements in annexure-1.
5.2.1.4  Observations:
5.2.1.4.1        The melting point is 168oC-172oC.
5.2.2        UV/VIS absorption Spectrophotometry:
5.2.2.1  Material and equipment:
5.2.2.1.1        UV/VIS Spectrophotometer.
5.2.2.1.2        Glassware (according to requirement).
5.2.2.1.3        Alcohol R.
5.2.2.2  Sample:
5.2.2.2.1        50.0mg.
5.2.2.3  Method:
5.2.2.3.1        Test solution:
5.2.2.3.1.1  Take a beaker of 100.0ml and add 50.0mg of sample in it.
5.2.2.3.1.2  Dissolve it in sufficient quantity of alcohol R.
5.2.2.3.1.3  And dilute it to 100.0ml with the same solvent.
5.2.2.3.2        Spectral range:
5.2.2.3.2.1  230-350nm.
5.2.2.3.3        Absorption maxima:
5.2.2.3.3.1  The solution shows 3 absorption maxima 253nm, 258nm and 264nm.
5.2.2.3.4        Operate the UV/VIS spectrophotometer according to the SOP.
5.2.2.3.5        Measure the absorbance of the resulting solution at the maximum wavelength 253nm, 258nm and 264nm.
5.2.2.3.6        Note down values of absorbance in annexure-2.
5.2.2.3.7        Calculate the absorbance ratio A258/A253 and A258/A264.
5.2.2.4  Observations:
5.2.2.4.1        Absorbance ratio A258/A253:
5.2.2.4.1.1  1.1 to 1.3.
5.2.2.4.2        Absorbance ratio A258/A264:
5.2.2.4.2.1  1.2 to 1.4.
5.2.3        Chlorides test:
5.2.3.1  Material and equipment:
5.2.3.1.1        Glassware (according to requirement).
5.2.3.1.2        Dilute nitric acid.
5.2.3.1.3        Purified water.
5.2.3.1.4        0.4ml of Silver nitrate R1.
5.2.3.1.5        Ammonia.
5.2.3.2  Sample:
5.2.3.2.1        Quantity of substance to be examined equivalent to about 2.0mg of chloride.
5.2.3.3  Method:
5.2.3.3.1        Take a test tube add in it 2.0ml of water with the help of pipette.
5.2.3.3.2        Dissolve in 2.0ml of water a quantity of the substance to be equivalent to about 2.0mg of chloride.
5.2.3.3.3        Acidify with dilute nitric acid.
5.2.3.3.4        And add 0.4ml of silver nitrate R1.
5.2.3.3.5        Shake and allow it to stand.
5.2.3.3.6        A curdled, white ppt is formed.
5.2.3.3.7        Centrifuge it in centrifugation machine, according to SOP.
5.2.3.3.8        The obtained ppt is wash with 3 quantities, each of 1ml, of water.
5.2.3.3.9        Carry out this operation rapidly is subdued light, degrading the fact that the supernatant solution may not become perfectly clear.
5.2.3.3.10    Suspend the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.2.3.4  Observations:
5.2.3.4.1        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  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-3.
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 alcohol.
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 50.0ml of alcohol and 5.0ml of 0.01M hydrochloric acid dissolve by using magnetic stirrer.
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.
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-4.
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-4.
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 29.18mg of Diphenhydramine hydrochloride C17H22ClNO.
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 / Diphenhydramine hydrochloride: 2015, pp. 773-774.
7.2  The British Pharmacopoeia. Vol V., Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0  ANNEXURES:
Annexure 1: Observations of Melting point apparatus.
Annexure 2: Observations of UV/VIS spectrophotometer.
Annexure 3: Observations of Percentage Loss of drying by using oven.
Annexure 4: Assay observations and calculations (Potentiometric titration).

Annexure: 1
Observations of Melting point apparatus
Sample = _____________
Time period = _____________
Sr.#
Initial (Ti)
(oC)
Final (Tf)
(oC)
Tf - Ti
(oC)












Average: _____________

Result: _________________

Remarks: _______________________________________________________________










Annexure: 2
Observations and Calculations of UV/VIS spectrophotometer
UV/VIS spectrophotometer
Model: _____________________________                             Date: _________________
OBSERVATIONS:
Thickness of cell:

Spectral range:
230-350nm.
Maxima absorption wavelength:
253nm, 258nm and 264nm.
Sample:

Other reagent used:


No. of obs.
Concentration
Wavelength
Absorbance









CALCULATIONS:
Absorbance ratio A258/A253 =
Absorbance ratio A258/A264=


Results: _______________
Remarks: ______________________________________________________________




Annexure: 3
Observations of percentage loss of drying by using Oven
Percentage loss of drying by using Oven
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
λ
Lambda
UV/VIS
Ultraviolet/ visible
w/v
Weight by volume
nm
Nanometer
Hrs.
Hours
A
Absorbance


No comments:

Post a Comment