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:
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=
_________________
Average % 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:
Plot a graph, volume used v/s millivolts and find out peak
of graph i.e. END POINT of blank titration.
Sample
titration:
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
|
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