SODIUM SESQUIHYDRATE SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of the Pantoprazole sodium sesquihydrate
from the Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1
Q.C Pharmacist.
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 powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (3 test
tubes, 1 spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Hexane.
5.1.2.1.4
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 3 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 hexane in test
tube 3 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 & 2 containing with purified water and ethanol (96%) are freely
soluble.
5.1.2.4.2
The sample in test
tube 3 containing with hexane is practically insoluble.
5.2 Identification
tests:
5.2.1
Sodium
test:
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware (1
crucible, 1 beaker, 2 test tubes, 1 glass rod, 1 funnel).
5.2.1.1.2
Bunsen burner.
5.2.1.1.3
2.0ml of 150g/L
solution of potassium carbonate.
5.2.1.1.4
4.0ml of potassium
pyroantimonate solution.
5.2.1.1.5
Ice water.
5.2.1.1.6
Purified water
(q.s)
5.2.1.2
Sample:
5.2.1.2.1
0.1g.
5.2.1.3
Method:
5.2.1.3.1
Take a test tube
and add 0.1g of sample in it.
5.2.1.3.2
Dissolve it with
2.0ml of purified water.
5.2.1.3.3
Add 2.0ml of the
150g/L solution of potassium carbonate
5.2.1.3.4
Heat it on Bunsen
burner till boiling.
5.2.1.3.5
No ppt is formed.
5.2.1.3.6
Add 4.0ml of
potassium pyroantimonate solution heat on burner till boiling.
5.2.1.3.7
Take a beaker of
ice water. And cool the test tube into it, if necessary rub inside of the test
tube with a glass rod.
5.2.1.3.8
Observe the
changes.
5.2.1.4
Observations:
5.2.1.4.1
A dense white
precipitate is formed.
5.3 Optical
rotation:
5.3.1
Material and equipment:
5.3.1.1
Polarimeter.
5.3.1.2
Analytical
weighing balance.
5.3.1.3
pH meter.
5.3.1.4
Glassware (1
beaker of 50.0ml, 1 stirrer, 1 spatula).
5.3.1.5
8g/L solution of
sodium hydroxide.
5.3.1.6
Purified water
(q.s).
5.3.2
Sample:
5.3.2.1
0.2g of sample.
5.3.3
Method:
5.3.3.1
Test
solution:
5.3.3.1.1
Take a beaker of
50.0ml and dissolve 0.2g of sample in 10.0ml of purified water.
5.3.3.1.2
Adjust pH
11.5-12.0 with 8g/L solution of sodium hydroxide by using pH meter. Operate pH meter
according to SOP
5.3.3.1.3
Dilute it to 20.0ml
with purified water.
5.3.3.2
Firstly clean the
Polarimeter with clean dry cloth, according to SOP
5.3.3.3
Operate the
Polarimeter according to SOP.
5.3.3.4
Fill the
Polarimeter tube with blank solution and determine the observed optical rotation.
5.3.3.5
Similarly, fill
the Polarimeter tube with sample solution and determine the observed optical
rotation.
5.3.3.6
Note down the
values in annexure-1.
5.3.3.7
Calculate the optical
rotation of substance by subtracting sample solution observed optical rotation
from the blank optical rotation.
Optical rotation
of substance = Blank solution - Sample solution.
5.3.4
Observations:
5.3.4.1
-0.4o
to +0.4o.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Potentiometer.
5.4.2
Material
and reagents:
5.4.2.1
80.0ml of anhydrous
acetic acid.
5.4.2.2
5.0ml of acetic
acid.
5.4.2.3
0.1M Perchloric
acid.
5.4.2.4
Crystal violet
solution (as indicator).
5.4.3
Sample:
5.4.3.1
0.200g.
5.4.4
Method
of analysis:
5.4.4.1 Take
a 100.0ml of beaker and add 0.200g of sample in it.
5.4.4.2 Add
80.0ml of anhydrous acetic acid in it and dissolve by using magnetic stirrer
i.e. SOP.
5.4.4.3 Add
5.0ml of acetic acid and dissolve by using magnetic stirrer for at least 10min.
5.4.4.4 Fill
the right hand side burette with titrant 0.1M Perchloric acid.
5.4.4.5 Carry
out a Potentiometric titration using crystal violet solution as an indicator.
5.4.4.6 Operate
potentiometer according to SOP.
5.4.4.7 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.
5.4.4.8 Plot
a graph, volume used v/s millivolts.
5.4.4.9 Find
out the END POINT.
5.4.4.10 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.4.4.11 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.4.4.12 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.4.4.13 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 Perchloric acid is equivalent to 20.27mg of Pantoprazole sodium
sesquihydrate C16H14F2N3NaO4S.
5.4.6
Limit:
5.4.6.1
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 II.,
Official Monograph / Pantoprazole sodium sesquihydrate: 2015, pp. 494-495.
8.0 ANNEXURES:
Annexure 1: Optical
rotation observations and calculations.
Annexure 2: Assay
observations and calculations (Potentiometric titration).
Annexure:
1
Optical
rotation observations and calculations
|
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.
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
|
|
Q.C
|
Quality
control
|
|
B.P
|
British
pharmacopoeia
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
q.s
|
Quantity
sufficient
|
|
M
|
Molar
|
|
g
|
Grams
|
|
v/s
|
Verses
|
|
%
|
Percentage
|
|
mV
|
Millivolts
|
|
oC
|
Degree
centigrade
|
|
ml
|
Milliliter
|
|
ppt
|
Precipitate
|
|
o
|
Degree
(angle)
|
|
l
|
Length
|
|
g
|
Grams
|
|
c
|
Concentration
(g/ml)
|
|
Min
|
Minutes
|
|
mg
|
Milligram
|
|
α
|
Alpha
|
|
λ
|
Lambda
|
|
T
|
Temperature
|
|
Sr.#
|
Serial
number
|
|
g/L
|
Grams
per liter
|