RABEPRAZOLE SODIUM METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Rabeprazole sodium 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
A white to
slightly yellowish white.
5.1.1.2
Crystalline solid.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (7 test
tubes, 1 spatula, 1 pipette).
5.1.2.1.2
Methanol.
5.1.2.1.3
Ethanol.
5.1.2.1.4
Chloroform.
5.1.2.1.5
Ethyl acetate.
5.1.2.1.6
Ether.
5.1.2.1.7
N-hexane.
5.1.2.1.8
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 7 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 methanol in
test tube 2 and observe.
5.1.2.3.4
Add Ethanol in
test tube 3 and observe
5.1.2.3.5
Add chloroform in
test tube 4 and observe.
5.1.2.3.6
Add ethyl acetate in
test tube 5 and observe.
5.1.2.3.7
Add ether in test
tube 6 and observe.
5.1.2.3.8
Add n-hexane in
test tube 7 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 & 2 containing with purified water and methanol is very soluble.
5.1.2.4.2
The sample in test
tube 3, 4 & 5 containing with ethanol, chloroform and ethyl acetate is soluble.
5.1.2.4.3
The sample in test
tube 6 & 7 containing with ether and n-hexane is insoluble.
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
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
Introduce the
sufficient quantity of sample into a capillary tube.
5.2.1.3.2
Set the apparatus
and immerse the capillary tube into the apparatus such that the closed end is
near the center of the bulb of thermometer.
5.2.1.3.3
Switch on the
melting point apparatus.
5.2.1.3.4
Operate the
melting point apparatus according to the SOP
5.2.1.3.5
Raise the
temperature of the apparatus.
5.2.1.3.6
Record the
temperature at which the last particle passes into the liquid phase.
5.2.1.3.7
Record
measurements in annexure-1.
5.2.1.4
Observations:
5.2.1.4.1
The melting point
is 140oC-141oC. (7.1)
5.2.2
Sodium
test:
5.2.2.1
Material and equipment:
5.2.2.1.1
Glassware (1
crucible, 1 beaker, 2 test tubes, 1 glass rod, 1 funnel).
5.2.2.1.2
Bunsen burner.
5.2.2.1.3
2.0ml of 150g/L
solution of potassium carbonate.
5.2.2.1.4
4.0ml of potassium
pyroantimonate solution.
5.2.2.1.5
Ice water.
5.2.2.1.6
Purified water
(q.s)
5.2.2.2
Sample:
5.2.2.2.1
0.1g.
5.2.2.3
Method:
5.2.2.3.1
Take a test tube
and add 0.1g of sample in it.
5.2.2.3.2
Dissolve it with
2.0ml of purified water.
5.2.2.3.3
Add 2.0ml of the
150g/L solution of potassium carbonate
5.2.2.3.4
Heat it on Bunsen
burner till boiling.
5.2.2.3.5
No ppt is formed.
5.2.2.3.6
Add 4.0ml of potassium
pyroantimonate solution heat on burner till boiling.
5.2.2.3.7
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.
5.2.2.3.8
Observe the
changes.
5.2.2.4
Observations:
5.2.2.4.1
A dense white
precipitate is formed. (7.2)
5.3 Assay:
5.3.1
Apparatus:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Potentiometer.
5.3.2
Material
and reagents:
5.3.2.1
80.0ml of
anhydrous acetic acid.
5.3.2.2
5.0ml of acetic
acid.
5.3.2.3
0.1M Perchloric
acid.
5.3.2.4
Crystal violet
solution (as indicator).
5.3.3
Sample:
5.3.3.1
0.200g.
5.3.4
Method
of analysis:
5.3.4.1 Take
a 100.0ml of beaker and add 0.200g of sample in it.
5.3.4.2 Add
80.0ml of anhydrous acetic acid in it and dissolve by using magnetic stirrer
i.e. SOP
5.3.4.3 Add
5.0ml of acetic acid and dissolve by using magnetic stirrer for at least 10min.
5.3.4.4 Fill
the right hand side burette with titrant 0.1M Perchloric acid.
5.3.4.5 Carry
out a Potentiometric titration using crystal violet solution as an indicator.
5.3.4.6 Operate
potentiometer according to SOP
5.3.4.7 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.
5.3.4.8 Plot
a graph, volume used v/s millivolts.
5.3.4.9 Find
out the END POINT.
5.3.4.10 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.3.4.11 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.3.4.12 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.3.4.13 Calculate
percentage purity of the sample by using formula:
%age
purity = volume used by substance x factor x 100
Weight of sample
5.3.5
Factor:
5.3.5.1 1ml
of 0.1M Perchloric acid is equivalent to 38.48mg of Rabeprazole sodium C18H20N3NaO3S.
5.3.6
Limit:
5.3.6.1
99.0% to 100.0%. (7.3)
6.0 REVISION LOG:
|
Revision No.
|
Effective Date
|
Reason
|
|
00
|
|
New SOP
|
7.0 REFERENCES:
7.1
A.C. Moffat, M.D.
Osselton and B. Widdop. Vol-2, Part-2/ Monographs: Rabeprazole in Clarke’s Analysis of Drugs and Poisons. Pharmaceutical
press. 4th edition, 2011.
7.2
The British
Pharmacopoeia. Vol V.,
Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
7.3
A.C. Moffat, M.D.
Osselton and B. Widdop. Vol-2, Part-2/ Monographs: Rabeprazole in Clarke’s Analysis of Drugs and Poisons. Pharmaceutical
press. 4th edition, 2011.
8.0 ANNEXURES:
Annexure 1: Observations
of Melting point apparatus.
Annexure 2: 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
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
|
|
v/s
|
Verses
|
|
mV
|
Millivolts
|
|
G
|
Grams
|
|
ml
|
Milliliter
|
|
oC
|
Degree
centigrade
|
|
mg
|
Milligram
|
|
M
|
Molar
|
|
%
|
Percentage
|
|
Ti
|
Initial
temperature
|
|
Tf
|
Final
temperature
|
|
Temp.
|
Temperature
|