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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:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












Plot a graph, volume used v/s millivolts and find out peak of graph i.e. END POINT of blank titration.
Sample titration:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












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


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