QUETIAPINE FUMERATE METHOD OF ANALYSIS SOP


QUETIAPINE FUMERATE METHOD OF ANALYSIS SOP

1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of Quetiapine Fumarate 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 powder.
5.1.2        Solubility:
5.1.2.1  Material and equipment:
5.1.2.1.1        Glassware (2 test tubes, spatula).
5.1.2.1.2        Purified water.
5.1.2.1.3        Anhydrous ethanol.
5.1.2.1.4        Methanol.
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, anhydrous ethanol in test tube 2 and methanol in test tube 3 in a small volume and observe the solubility of the sample.
5.1.2.4  Observations:
5.1.2.4.1        The sample in test tube 1, 2 & 3 containing with purified water, anhydrous ethanol and methanol are slightly soluble.
5.2  Loss on drying:
5.2.1        Material and equipment:
5.2.1.1  Glassware (according to requirement).
5.2.1.2  Analytical weighing balance.
5.2.1.3  Oven.
5.2.2        Sample:
5.2.2.1  1.0g.
5.2.3        Method:
5.2.3.1  Weigh 1.0g of the test sample.
5.2.3.2  Set the oven apparatus. Operate it according to the SOP.
5.2.3.3  Place the sample into the tray and dry it.
5.2.3.4  Set the temperature of oven at 105oC for at least 45 minutes.
5.2.3.5  And wait till the sample loses its moisture.
5.2.3.6  After 45 minutes weigh the sample again by using analytical weighing balance i.e. the final weight.
5.2.3.7  Note down readings on given Annexure-1.
5.2.4        Observation:
5.2.4.1  Maximum 0.5%.
5.3  Assay:
5.3.1        Quetiapine fumarate:
5.3.1.1  Apparatus:
5.3.1.1.1        Glassware (according to requirement).
5.3.1.1.2        Potentiometer.
5.3.1.2  Material and reagents:
5.3.1.2.1        40.0ml of anhydrous acetic acid.
5.3.1.2.2        0.1M Perchloric acid.
5.3.1.2.3        Crystal violet solution.
5.3.1.3  Sample:
5.3.1.3.1        0.170g.
5.3.1.4  Method of analysis:
5.3.1.4.1        Take a 100.0ml of beaker and take 0.170g of sample in it.
5.3.1.4.2        Add 40.0ml of anhydrous acetic acid. Dissolve it by using magnetic stirrer i.e. SOP.
5.3.1.4.3        Fill the right hand side burette with titrant 0.1M Perchloric acid.
5.3.1.4.4        Carry out a Potentiometric titration using crystal violet solution as an indicator.
5.3.1.4.5        Operate potentiometer according to SOP.
5.3.1.4.6        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.
5.3.1.4.7        Plot a graph, volume used v/s millivolts.
5.3.1.4.8        Find out the END POINT.
5.3.1.4.9        Peak of graph indicates END POINT i.e. the point at which maximum millivolts. Note down volume used at that point.
5.3.1.4.10    Perform blank titration without using sample. Similarly, as sample titration performed. Record observations in annexure-2.
5.3.1.4.11    Calculate volume used by substance by using formula:
                                         Volume used by substance = Blank titration - Sample titration.
5.3.1.4.12    Calculate percentage purity of the sample by using formula:
                                               %age purity = volume used by substance x factor x 100
                                Weight of sample
5.3.1.5  Factor:
5.3.1.5.1        1ml of 0.1M Perchloric acid is equivalent to 22.08mg of Quetiapine fumerate C46H54N6O8S2.
5.3.1.6  Limit:
5.3.1.6.1        99.0% to 101.0% (dried substance).
5.3.2        Fumaric acid:
5.3.2.1  Apparatus:
5.3.2.1.1        Glassware (according to requirement).
5.3.2.1.2        Potentiometer.
5.3.2.2  Material and reagents:
5.3.2.2.1        Methanol.
5.3.2.2.2        Purified water.
5.3.2.2.3        0.1M sodium hydroxide.
5.3.2.2.4        Thymolphthalein solution.
5.3.2.3  Sample:
5.3.2.3.1        0.350g.
5.3.2.4  Method of analysis:
5.3.2.4.1        Take a 100.0ml of beaker and take 0.350g of sample in it.
5.3.2.4.2        Add 70.0ml of a mixture of equal volumes of methanol and purified water. Dissolve it by using magnetic stirrer i.e. SOP.
5.3.2.4.3        Fill the right hand side burette with titrant 0.1M sodium hydroxide.
5.3.2.4.4        Carry out a Potentiometric titration using Thymolphthalein solution as an indicator.
5.3.2.4.5        Operate potentiometer according to SOP.
5.3.2.4.6        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-3.
5.3.2.4.7        Plot a graph, volume used v/s millivolts.
5.3.2.4.8        Find out the END POINT.
5.3.2.4.9        Peak of graph indicates END POINT i.e. the point at which maximum millivolts. Note down volume used at that point.
5.3.2.4.10    Perform blank titration without using sample. Similarly, as sample titration performed. Record observations in annexure-3.
5.3.2.4.11    Calculate volume used by substance by using formula:
                                         Volume used by substance = Blank titration - Sample titration.
5.3.2.4.12    Calculate percentage purity of the sample by using formula:
                                               %age purity = volume used by substance x factor x 100
                                Weight of sample
5.3.2.5  Factor:
5.3.2.5.1        1ml of 0.1M sodium hydroxide is equivalent to 5.804mg of Fumaric acid C4H4O4.
5.3.2.6  Limit:
5.3.2.6.1        12.5% to 13.8% (dried 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 /Quetiapine Fumarate: 2015, pp. 709-711.
8.0  ANNEXURES:
Annexure 1: Observations of Percentage Loss of drying by using oven.
Annexure 2: Assay observations and calculations (Potentiometric titration) for Quetiapine fumarate.
Annexure 3: Assay observations and calculations (Potentiometric titration) for Fumaric acid.
                                                             
Annexure: 1
Observations of percentage loss of drying by using Oven
Percentage loss of drying by using Oven
Apparatus: ____________________
Temperature: __________________
Weight of Sample = _____________
Time period = _____________
Pressure= _________________
Sr.#
Time (min)
Weight of sample (g)
% Loss of Moisture
Initial weight
Final weight















Average % Loss of Moisture: _____________

% Loss of Moisture:






Remarks: _______________________________________________________________




Annexure: 2
Assay observations and calculations (Potentiometric titration) for Quetiapine fumarate
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: ____________________________________________________________











Annexure: 3
Assay observations and calculations (Potentiometric titration) for Fumaric acid
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
Q.C
Quality control
B.P
British pharmacopoeia
M
Molar
g
Grams
ml
Milliliter
mg
Milligram
%
Percentage
Vol
Volume
QCA
Quality control active ingredient
F
Format
mV
Millivolts
v/s
Verses
Min
Minutes


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