SUCRALFATE METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of the Sucralfate from the
Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1
Q.C Analysts.
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, amorphous powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (4 test
tubes, 1 spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
Dilute solutions
of mineral acid and alkali hydroxide.
5.1.2.1.5
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 4 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.
5.1.2.3.5
Add dilute
solutions of mineral acid and alkali hydroxide in test tube 4 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1, 2 & 3 containing with purified water, ethanol (96%) & Methylene
chloride is practically insoluble.
5.1.2.4.2
The sample in test
tube 4 containing with dilute solutions of mineral acid and alkali hydroxide is
dissolved.
5.2 Identification
tests:
5.2.1
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Burner.
5.2.1.1.3
10.0ml of 0.1M
hydrochloric acid.
5.2.1.1.4
0.1M sodium
hydroxide.
5.2.1.1.5
0.15ml of freshly
prepared copper sulphate solution.
5.2.1.1.6
2.0ml of freshly
prepared dilute sodium hydroxide.
5.2.1.1.7
4.0ml of dilute
hydrochloric acid.
5.2.1.1.8
4.0ml of dilute
sodium hydroxide solution.
5.2.1.2
Sample:
5.2.1.2.1
2.0g.
5.2.1.3
Method:
5.2.1.3.1
Take a test tube
and add 2.0g of sample in it and add 10.0ml of 0.1M hydrochloric acid and boil
it on burner.
5.2.1.3.2
Cool it and
neutralize with 0.1M sodium hydroxide.
5.2.1.3.3
Take another test
tube add 5.0ml of the above solution.
5.2.1.3.4
Add 0.15ml of
freshly prepared copper sulphate solution and 2.0ml of freshly prepared dilute
sodium hydroxide.
5.2.1.3.5
The solution is
blue and clear.
5.2.1.3.6
Boil on burner the
solution remains blue and clear after boiling.
5.2.1.3.7
To the hot
solution add 4.0ml of dilute hydrochloric acid and boil for 1 min on burner.
5.2.1.3.8
Add 4.0ml of
dilute sodium hydroxide solution.
5.2.1.3.9
Observe the
changes.
5.2.1.4
Observations:
5.2.1.4.1
An orange ppt is
formed, immediately.
5.2.2
Aluminium
test:
5.2.2.1
Material and equipment:
5.2.2.1.1
Glassware
(according to requirement).
5.2.2.1.2
Burner.
5.2.2.1.3
0.5ml of dilute
hydrochloric acid.
5.2.2.1.4
0.5ml of
thioacetamide reagent.
5.2.2.1.5
Dilute sodium
hydroxide solution (q.s).
5.2.2.1.6
Ammonium chloride
solution (q.s).
5.2.2.1.7
Purified water
(q.s).
5.2.2.2
Sample:
5.2.2.2.1
15.0mg.
5.2.2.3
Method:
5.2.2.3.1
Take a test tube
and add 15.0mg of sample in it.
5.2.2.3.2
Dissolve it in a
mixture of 0.5ml of dilute hydrochloric acid and 2.0ml of purified water.
5.2.2.3.3
Add about 0.5ml of
dilute hydrochloric acid and about 0.5ml of thioacetamide reagent.
5.2.2.3.4
No ppt is formed.
5.2.2.3.5
Add drop wise
dilute sodium hydroxide solution.
5.2.2.3.6
A gelatinous white
ppt is formed.
5.2.2.3.7
Add further dilute
sodium hydroxide solution
5.2.2.3.8
Observe the change
that gelatinous white ppt is dissolved.
5.2.2.3.9
Gradually add
ammonium chloride solution.
5.2.2.3.10 Observe
the changes.
5.2.2.4
Observations:
5.2.2.4.1
The gelatinous
white ppt is re-formed.
5.3 Assay:
5.3.1
Aluminium:
5.3.1.1
Apparatus:
5.3.1.1.1
Glassware
(according to requirement).
5.3.1.1.2
Analytical
weighing balance.
5.3.1.1.3
Water bath.
5.3.1.1.4
Magnetic stirrer.
5.3.1.1.5
Titration
apparatus.
5.3.1.2
Material
and reagents:
5.3.1.2.1
10.0ml of 6M
hydrochloric acid.
5.3.1.2.2
10.0ml of 0.1M
sodium edetate.
5.3.1.2.3
Ammonium acetate
solution.
5.3.1.2.4
Dilute acetic
acid.
5.3.1.2.5
25.0ml of ethanol
(96%).
5.3.1.2.6
1.0ml of freshly
prepared 0.25g/L solution of dithizone in ethanol (96%).
5.3.1.2.7
0.1M zinc sulfate.
5.3.1.2.8
Purified water
(q.s).
5.3.1.3
Sample:
5.3.1.3.1
1.0g
5.3.1.4 Method of
analysis:
5.3.1.4.1
Sample titration:
5.3.1.4.1.1 Take
a beaker of 50.0ml and add 0.1g of sample in it.
5.3.1.4.1.2 Disperse
the sample in 10.0ml of 6M hydrochloric acid.
5.3.1.4.1.3 Heat
it with continuous stirring in a water bath at 70oC for 5min.
5.3.1.4.1.4 Cool
it to room temperature.
5.3.1.4.1.5 Take
a 250.0ml of volumetric flask and transfer quantitatively to a volumetric flask
and dilute it to 250.0ml with purified water, mix it.
5.3.1.4.1.6 Filter
the solution by using filter paper and 1000.0ml of beaker. Discard the 1st
portion of the filtrate.
5.3.1.4.1.7 Take
a conical flask and add 10.0ml of solution in it.
5.3.1.4.1.8 Add
10.0ml of 0.1M sodium edetate and 30.0ml of mixture of equal volumes of ammonium
acetate solution and dilute acetic acid.
5.3.1.4.1.9 Heat
it on water bath at 70oC for 5min, and then cool.
5.3.1.4.1.10
Add 25.0ml of
ethanol (96%) and 1.0ml of a freshly prepared 0.25g/L solution of dithizone in
ethanol (96%).
5.3.1.4.1.11
Set titration
apparatus.
5.3.1.4.1.12
Fill titrant 0.1M
zinc sulfate in burette.
5.3.1.4.1.13
Titrate the excess
of sodium edetate with 0.1M zinc sulfate until the colour changes to pink.
5.3.1.4.1.14
Note down the volume
used as shown in Annexure-1.
5.3.1.4.1.15
And take average.
5.3.1.4.2
Blank titration:
5.3.1.4.2.1 Take
a beaker of 50.0ml and add 10.0ml of 6M hydrochloric acid.
5.3.1.4.2.2 Heat
it with continuous stirring in a water bath at 70oC for 5min.
5.3.1.4.2.3 Cool
it to room temperature.
5.3.1.4.2.4 Take
a 250.0ml of volumetric flask and transfer quantitatively to a volumetric flask
and dilute it to 250.0ml with purified water, mix it.
5.3.1.4.2.5 Filter
the solution by using filter paper and 1000.0ml of beaker. Discard the 1st
portion of the filtrate.
5.3.1.4.2.6 Take
a conical flask and add 10.0ml of solution in it.
5.3.1.4.2.7 Add
10.0ml of 0.1M sodium edetate and 30.0ml of mixture of equal volumes of ammonium
acetate solution and dilute acetic acid.
5.3.1.4.2.8 Heat
it on water bath at 70oC for 5min, and then cool.
5.3.1.4.2.9 Add
25.0ml of ethanol (96%) and 1.0ml of a freshly prepared 0.25g/L solution of
dithizone in ethanol (96%).
5.3.1.4.2.10 Set
titration apparatus.
5.3.1.4.2.11 Fill
titrant 0.1M zinc sulfate in burette.
5.3.1.4.2.12 Titrate
the excess of sodium edetate with 0.1M zinc sulfate until the colour changes to
pink.
5.3.1.4.2.13 Note
down the volume used as shown in Annexure-1.
5.3.1.4.2.14 And
take average.
5.3.1.4.3
Calculate
percentage purity.
5.3.1.4.4
Calculations:
5.3.1.4.4.1 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.
5.3.1.4.4.2 For
percentage purity use formula:
%age purity = volume
used by substance x factor x 100
Weight of sample
5.3.1.4.4.3 Put
values and calculate %age purity.
5.3.1.5 Factor:
5.3.1.5.1
1ml of 0.1M sodium
edetate is equivalent to 2.689mg of aluminium Al.
5.3.1.6 Limit:
5.3.1.6.1
16.5% to 18.5%.
6.0 REVISION LOG:
|
Revision No.
|
Effective Date
|
Reason
|
|
00
|
|
New SOP
|
7.0 REFERENCES:
7.1
The British
Pharmacopoeia. Vol II.,
Official Monograph / Sucralfate: 2015, pp. 925-926.
8.0 ANNEXURES:
Annexure 1: Assay
observations and calculations.
Annexure:
1
Assay
observations and calculations (Acid-base titration)
|
Acid-base titration
Indicator: ___________________
Weight of sample: ____________
Factor: 5.832mg.
Titrant: _____________________
Sample
titration
Average volume: _________________
Blank
titration
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
|
|
Sr.#
|
Serial
number
|
|
Q.C
|
Quality
control
|
|
%
|
Percentage
|
|
q.s
|
Quantity
sufficient
|
|
Ppt
|
Precipitate
|
|
G
|
Grams
|
|
Ml
|
Milliliter
|
|
M
|
Molar
|
|
g/L
|
Grams
per liter
|
|
mg
|
Milligram
|
|
oC
|
Degree
centigrade
|
|
vi
|
Initial
volume
|
|
vf
|
Final
volume
|
|
B.P
|
British
pharmacopoeia
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|