1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Dextromethorphan hydrobromide 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 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
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 purified water is sparingly 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
Specific optical rotation:
5.2.1.1 Material and equipment:
5.2.1.1.1
Polarimeter.
5.2.1.1.2
Analytical
weighing balance.
5.2.1.1.3
Glassware
(1 beaker of 50.0ml, 1 stirrer, 1 spatula, 1 glass rod).
5.2.1.1.4
0.1Mhydrochloric
acid.
5.2.1.2 Sample:
5.2.1.2.1
0.2g.
5.2.1.3 Method:
5.2.1.3.1
Take
a beaker of 50.0ml and add 0.2g of sample in it.
5.2.1.3.2
Dissolve
it in 0.1Mhydrochloric acid (approx. 5.0ml) by using glass rod.
5.2.1.3.3
Dilute
it to 10.0ml with the same acid.
5.2.1.3.4
Firstly
clean the Polarimeter with clean dry cloth, according to SOP
5.2.1.3.5
Operate
the Polarimeter according to SOP
5.2.1.3.6
Fill
the Polarimeter tube with blank solution and determine the observed optical
rotation.
5.2.1.3.7
Similarly,
fill the Polarimeter tube with sample solution and determine the observed
optical rotation.
5.2.1.3.8
Note
down the values in annexure-1.
5.2.1.3.9
Calculate
the specific optical rotation by using formula:
[α]λ T = α/lc
5.2.1.4 Observations:
5.2.1.4.1
-32.5
to -35.5.
5.2.2
Bromides test:
5.2.2.1 Material and equipment:
5.2.2.1.1
Glassware
(according to requirement).
5.2.2.1.2
Centrifuge
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
1.5ml
of Ammonia.
5.2.2.2 Sample:
5.2.2.2.1
Quantity
of substance to be examined equivalent to about 3.0mg of bromide.
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 3.0mg
of bromide.
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, pale yellow ppt is formed.
5.2.2.3.7
Centrifuge
it in centrifugation machine, according to SOP.
5.2.2.3.8
The
obtained ppt is wash with 3 times 1.0ml quantities of purified 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.
5.2.2.3.11 Observe the changes.
5.2.2.4 Observations:
5.2.2.4.1
The
precipitate dissolves with difficulty.
5.3 Assay:
5.3.1
Apparatus:
5.3.1.1 Glassware (according to requirement).
5.3.1.2 Potentiometer.
5.3.1.3 Magnetic stirrer.
5.3.2
Material and reagents:
5.3.2.1 5.0ml of 0.01M hydrochloric acid.
5.3.2.2 20.0ml of ethanol (96%).
5.3.2.3 0.1M sodium hydroxide.
5.3.2.4 Thymolphthalein solution (as indicator).
5.3.3
Sample:
5.3.3.1 0.3g.
5.3.4
Method of analysis:
5.3.4.1 Take a 100.0ml of beaker and take 0.3g of
sample in it.
5.3.4.2 Add a mixture of 5.0ml of 0.01M
hydrochloric acid and 20.0ml of ethanol (96%) dissolve by using magnetic
stirrer.
5.3.4.3 Fill the right hand side burette with
titrant 0.1M sodium hydroxide.
5.3.4.4 Carry out a Potentiometric titration using
thymolphthalein solution (as indicator).
5.3.4.5 Operate potentiometer according to SOP.
5.3.4.6 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.
5.3.4.7 Plot a graph, volume used v/s millivolts.
5.3.4.8 Find out the END POINT. Read the volume
added between the 2 points of inflexion.
5.3.4.9 Peak of graph indicates END POINT i.e. the
point at which maximum millivolts. Note down volume used at that point.
5.3.4.10 Perform blank titration without using
sample. Similarly, as sample titration performed. Record observations in
annexure-2.
5.3.4.11 Calculate volume used by substance by
using formula:
Volume
used by substance = Blank titration - Sample titration.
5.3.4.12 Calculate percentage purity of the sample
by using formula:
%age
purity = volume used by substance x factor x 100
Weight of sample
5.3.5
Factor:
5.3.5.1 1ml of 0.1M sodium hydroxide is equivalent
to 35.23mg of dextromethorphan hydrobromide C18H26BrNO.
5.3.6
Limit:
5.3.6.1 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 I., Official Monograph / Dextromethorphan hydrobromide: 2015, pp. 714-716.
7.2 The British Pharmacopoeia. Vol V., Official Monograph /Qualitative
Reactions and Tests: 2015, pp. 266-270.
8.0 ANNEXURES:
Annexure 1: Specific
optical rotation observations and calculations.
Annexure 2: Assay
observations and calculations (Potentiometric titration).
Annexure: 1
Specific
optical rotation observations and calculations
Specific optical
rotation
Instrument:
___________________
Date: _______________
Model:
_______________________ Length
of Polarimeter tube: ________________
Sample:
________________________________g.
Solvent:
________________________________ml.
Concentration
of sample solution: ____________g/ml.
Blank solution:
Average: _______________
Optical
rotation of blank solution: _______________
Sample solution:
Average: _______________
Optical
rotation of sample solution: ______________
Optical
rotation of substance = Blank solution - Sample solution.
Specific
optical rotation of sample solution by using formula:
[α]λ T = α/lc
Result: ________________
Remarks:
___________________________________________________________
|
Annexure:
2
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
|
%
|
Percentage
|
B.P
|
British
pharmacopoeia
|
g
|
Grams
|
ml
|
Milliliter
|
oC
|
Degree
centigrade
|
mg
|
Milligram
|
g
|
Grams
|
M
|
Molar
|
Vol
|
Volume
|
vi
|
Initial
volume
|
vf
|
Final
volume
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|
Ti
|
Initial
temperature
|
Tf
|
Final
temperature
|
Temp.
|
Temperature
|
v/s
|
Verses
|
mV
|
Millivolts
|
o
|
Degree
(angle)
|
l
|
Length
|
c
|
Concentration
(g/ml)
|
g/ml
|
Gram
per milliliter
|
α
|
Alpha
|
λ
|
Lambda
|
g/L
|
Grams
per liter
|