EPHEDRINE SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Ephedrine 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.
5.1.1.2
Crystalline powder
or colorless crystals.
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 anhydrous
ethanol 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 soluble.
5.1.2.4.2
The sample in test
tube 2 containing with anhydrous ethanol is very 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
Magnetic stirrer.
5.2.1.1.4
Glassware (1
beaker of 50.0ml, 1 stirrer, 1 spatula).
5.2.1.1.5
15.0ml of dilute
hydrochloric acid.
5.2.1.1.6
Purified water.
5.2.1.2
Sample:
5.2.1.2.1
2.25g
5.2.1.3
Method:
5.2.1.3.1
Take a beaker of
50.0ml and add 2.25g of sample in it.
5.2.1.3.2
Dissolve it in
15.0ml of dilute hydrochloric acid by using magnetic stirrer operate according
to SOP No. BM/QCEO/SOP007-00.
5.2.1.3.3
And then dilute it
to 50.0mlwith purified water.
5.2.1.3.4
Firstly clean the
Polarimeter with clean dry cloth, according to SOP No. BM/QCEC/SOP031-00.
5.2.1.3.5
Operate the
Polarimeter according to SOP No. BM/QCEO/SOP030-00.
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 with reference to anhydrous substance by using
formula:
[α]λ T = α/lc
5.2.1.4
Observations:
5.2.1.4.1
The specific
optical rotation is -41 to -43.
5.2.2
5.2.2.1
Material and equipment:
5.2.2.1.1
Glassware (1 test
tube, 1 pipette).
5.2.2.1.2
Analytical
weighing balance.
5.2.2.1.3
0.2ml of strong
sodium hydroxide solution.
5.2.2.1.4
0.2ml of copper
sulfate solution.
5.2.2.1.5
2.0ml of ether.
5.2.2.1.6
1.0ml of purified water.
5.2.2.2
Sample:
5.2.2.2.1
10.0mg.
5.2.2.3
Method:
5.2.2.3.1
Take a test tube
and add 10.0mg of sample in it with 1.0ml of purified water, dissolve it.
5.2.2.3.2
Add 0.2ml of
strong sodium hydroxide solution and 0.2ml of copper sulfate solution
5.2.2.3.3
Observe the
changes.
5.2.2.3.4
A violet colour is
produced.
5.2.2.3.5
Add 2.0ml of ether
and shake it.
5.2.2.3.6
Observe the
changes.
5.2.2.4
Observations:
5.2.2.4.1
The ether layer is
purple but, the aqueous layer will be blue.
5.3 Assay:
5.3.1
Apparatus:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Titration
apparatus.
5.3.2
Material
and reagents:
5.3.2.1
5.0ml of Alcohol.
5.3.2.2
20.0ml of 0.1M
hydrochloric acid.
5.3.2.3
0.05ml of methyl
orange red (as indicator).
5.3.2.4
0.1M sodium
hydroxide.
5.3.3
Sample:
5.3.3.1
0.2g.
5.3.4
Method
of analysis:
5.3.4.1 Sample
titration:
5.3.4.1.1
Take a flask and
take in it 0.2g of sample.
5.3.4.1.2
Dissolve it in 5.0ml
of Alcohol by using glass rod.
5.3.4.1.3
Add 20.0ml of 0.1M
hydrochloric acid.
5.3.4.1.4
Set titration
apparatus.
5.3.4.1.5
Use 0.05ml of
methyl orange red, as indicator.
5.3.4.1.6
Titrate with 0.1M
sodium hydroxide, until a yellow colour is obtained.
5.3.4.1.7
Note down the
volume used as shown in Annexure-2.
5.3.4.1.8
Take 3 readings at
least and take average.
5.3.4.2 Blank
titration:
5.3.4.2.1
Take a flask and
take in it 5.0ml of Alcohol.
5.3.4.2.2
Add 20.0ml of 0.1M
hydrochloric acid.
5.3.4.2.3
Set titration
apparatus.
5.3.4.2.4
Use 0.05ml of
methyl orange red, as indicator.
5.3.4.2.5
Titrate with 0.1M
sodium hydroxide, until a yellow colour is obtained.
5.3.4.2.6
Note down the
volume used as shown in Annexure-2.
5.3.4.2.7
Take 3 readings at
least and take average.
5.3.4.3 Calculate
percentage purity.
5.3.4.4 Calculations:
5.3.4.4.1
After taking
average volume of both blank titration and sample titration. Calculate the
volume used by the examined substance by using formula:
Volume used by
substance = Blank titration - Sample titration.
5.3.4.4.2
For percentage
purity use formula:
%age purity = volume
used by substance x factor x 100
Weight of sample
5.3.4.4.3
Put values and
calculate %age purity.
5.3.5
Factor:
5.3.5.1 1ml
of 0.1M hydrochloric acid is equivalent to 16.52mg of ephedrine, C10H15NO2.
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 /Ephedrine: 2015, pp. 848-849.
8.0 ANNEXURES:
Annexure 1: Specific
optical rotation observations and calculations.
Annexure 2: Observations
and calculations of assay.
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
Observations
and calculations of assay.
Indicator:
___________________
Weight
of sample: ____________
Factor: ____________
Titrant:
_____________________
Sample titration
|
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
|
1.
|
|
|
|
|
2.
|
|
|
|
|
3.
|
|
|
|
Average volume: _________________
Blank titration
|
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
|
1.
|
|
|
|
|
2.
|
|
|
|
|
3.
|
|
|
|
Average volume: _________________
Calculations:
Volume used by substance = Blank
titration - Sample titration.
%age purity = volume used by
substance x factor x 100
Weight of sample
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
|
|
g
|
Grams
|
|
ml
|
Milliliter
|
|
oC
|
Degree
centigrade
|
|
mg
|
Milligram
|
|
M
|
Molar
|
|
vi
|
Initial
volume
|
|
vf
|
Final
volume
|
|
Temp.
|
Temperature
|
|
o
|
Degree
(angle)
|
|
l
|
Length
|
|
c
|
Concentration
(g/ml)
|
|
g/ml
|
Gram
per milliliter
|
|
α
|
Alpha
|
|
λ
|
Lambda
|