CARBOCISTEINE SOP



CARBOCISTEINE SOP

1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Carbocisteine 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.
5.1.1.2  Crystalline 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        Dilute mineral acid (HCl, HNO3 or H2SO4).
5.1.2.1.3        Dilute solution of alkali hydroxide (NaOH, Ca(OH)2)
5.1.2.1.4        Alcohol [Ethanol (96%)].
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 alcohol in test tube 2 and observe.
5.1.2.3.4        Add dilute mineral acid in test tube 3 and observe.
5.1.2.3.5        Add dilute solution of 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 containing with purified water and alcohol is insoluble respectively.
5.1.2.4.2        The sample in test tube 3 & 4 containing with dilute mineral acid and dilute solution of alkali hydroxide is dissolved respectively.
5.2  Solution S:
5.2.1        Material and equipment:
5.2.1.1  Glassware (1 100.0ml of beaker, 1 spatula, 1 glass rod, 1 pipette).
5.2.1.2  Analytical weighing balance.
5.2.1.3  Magnetic stirrer.
5.2.1.4  Purified water.
5.2.1.5  2.5ml of strong sodium hydroxide solution.
5.2.1.6  1.0M sodium hydroxide.
5.2.2        Sample:
5.2.2.1  5.0g.
5.2.3        Preparation of solution S:
5.2.3.1  Take a beaker of 100.0ml and disperse sample 0.5g in 20.0ml of purified water.
5.2.3.2  Add in it drop-wise with shaking 2.5ml of strong sodium hydroxide solution.
5.2.3.3  Adjust the pH 6.3 with 1.0M sodium hydroxide.
5.2.3.4  And dilute it to 50.0ml with purified water.
5.3  Identification tests:
5.3.1        Specific optical rotation:
5.3.1.1  Material and equipment:
5.3.1.1.1        Polarimeter.
5.3.1.1.2        Analytical weighing balance.
5.3.1.1.3        Glassware (1 beaker of 50.0ml, 1 stirrer, 1 spatula).
5.3.1.1.4        Methanol.
5.3.1.2  Sample:
5.3.1.2.1        Solution S.
5.3.1.3  Method:
5.3.1.3.1        Perform the test on the solution S.
5.3.1.3.2        Firstly clean the Polarimeter with clean dry cloth,
5.3.1.3.3        Operate the Polarimeter
5.3.1.3.4        Fill the Polarimeter tube with blank solution and determine the observed optical rotation.
5.3.1.3.5        Similarly, fill the Polarimeter tube with sample solution (i.e solution S) and determine the observed optical rotation.
5.3.1.3.6        Note down the values in annexure-1.
5.3.1.3.7        Calculate the specific optical rotation by using formula:
[α]λ T = α/lc
5.3.1.4  Observations:
5.3.1.4.1        -32.5 to -35.5.
5.3.2         
5.3.2.1  Material and equipment:
5.3.2.1.1        Glassware (1 test tube, 1 pipette).
5.3.2.1.2        Analytical weighing balance.
5.3.2.1.3        Water-bath.
5.3.2.1.4        4.5ml of dilute sodium hydroxide solution.
5.3.2.1.5        1.0ml of a 25g/L solution of sodium nitroprusside.
5.3.2.2  Sample:
5.3.2.2.1        0.1g.
5.3.2.3  Method:
5.3.2.3.1        Take a test tube and add 0.1g of sample in it with 4.5ml of dilute sodium hydroxide solution, dissolve it.
5.3.2.3.2        Heat on water-bath for 10min. And cool it then.
5.3.2.3.3        Add 1.0ml of a 25g/L solution of sodium nitroprusside.
5.3.2.3.4        Observe the changes.
5.3.2.4  Observations:
5.3.2.4.1        A dark red colour is produced, which changes to brown and then to yellow within a few minutes.
5.4  Loss on drying:
5.4.1        Material and equipment:
5.4.1.1  Glassware (according to requirement).
5.4.1.2  Analytical weighing balance.
5.4.1.3  Oven.
5.4.2        Sample:
5.4.2.1  1.0g.
5.4.3        Method:
5.4.3.1  Weigh 1.0g of the test sample.
5.4.3.2  Set the oven apparatus. Operate it.
5.4.3.3  Place the sample into the tray and dry it.
5.4.3.4  Set the temperature of oven at 105oC for 2h.
5.4.3.5  And wait till the sample loses its moisture.
5.4.3.6  After 2h weigh the sample again by using analytical weighing balance i.e. the final weight.
5.4.3.7  Note down readings on given Annexure-2.
5.4.4        Observation:
5.4.4.1  NMT 0.5%.
5.5  Assay:
5.5.1        Apparatus:
5.5.1.1  Glassware (according to requirement).
5.5.1.2  Potentiometer.
5.5.1.3  Magnetic stirrer.
5.5.2        Material and reagents:
5.5.2.1  10.0ml of anhydrous formic acid.
5.5.2.2  50.0ml of anhydrous acetic acid.
5.5.2.3  0.1M Perchloric acid.
5.5.2.4  Crystal violet solution (as indicator).
5.5.3        Sample:
5.5.3.1  0.15g.
5.5.4        Method of analysis:
5.5.4.1  Take a 100.0ml of beaker and take 0.15g of sample in it.
5.5.4.2  Add 10.0ml of anhydrous formic acid in it and dissolve with slight heating and shake until dissolution is complete by using magnetic stirrer.
5.5.4.3  Fill the right hand side burette with titrant 0.1M Perchloric acid.
5.5.4.4  Carry out a Potentiometric titration using crystal violet solution as an indicator.
5.5.4.5  Operate potentiometer.
5.5.4.6  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.
5.5.4.7  Plot a graph, volume used v/s millivolts.
5.5.4.8  Find out the END POINT.
5.5.4.9  Peak of graph indicates END POINT i.e. the point at which maximum millivolts. Note down volume used at that point.
5.5.4.10 Perform blank titration without using sample. Similarly, as sample titration performed. Record observations in annexure-3.
5.5.4.11    Calculate volume used by substance by using formula:
Volume used by substance = Blank titration - Sample titration.
5.5.4.12    Calculate percentage purity of the sample by using formula:
%age purity = volume used by substance x factor x 100
                             Weight of sample
5.5.5        Factor:
5.5.5.1  1ml of 0.1M Perchloric acid is equivalent to 17.92mg of Carbocisteine C5H9NO4S.
5.5.6        Limit:
5.5.6.1  98.5% to 101.0% (dried substance).
6.0  REVISION LOG:
Revision No.
Effective Date
Reason
00

New SOP
7.0  REFERENCES:
7.1  The British Pharmacopoeia. Vol I., Official Monograph /Carbocisteine: 2015, pp. 408-409.
8.0  ANNEXURES:
Annexure 1: Specific optical rotation observations and calculations.
Annexure 2: Observations of Percentage Loss of drying by using oven.
Annexure 3: Assay observations and calculations (Potentiometric titration).
                                                        










                                                         Annexure: 1
Specific optical rotation observations and calculations
Specific optical rotation
Instrument: ___________________                                              Date: _______________
Model: _______________________        Length of Polarimeter tube: ________________
Sample: ________________________________g.
Solvent: ________________________________ml.
Concentration of sample solution: ____________g/ml.
Blank solution:
Sr.#
Blank solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of blank solution: _______________
Sample solution:
Sr.#
Sample solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of sample solution: ______________
Optical rotation of substance = Blank solution - Sample solution.



Specific optical rotation of sample solution by using formula:
[α]λ T = α/lc






                                                                      Result: ________________
Remarks: ___________________________________________________________











                                              






Annexure: 2
Observations of percentage loss of drying by using Oven
Percentage loss of drying by using Oven
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: 3
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
%
Percentage
B.P
British pharmacopoeia
g
Grams
ml
Milliliter
oC
Degree centigrade
mg
Milligram
g
Grams
M
Molar
h
Hour
Vol
Volume
vi
Initial volume
vf
Final volume
QCA
Quality control active ingredient
F
Format
Ti
Initial temperature
Tf
Final temperature
Temp.
Temperature
v/s
Verses
mV
Millivolts
o
Degree (angle)
l
Length
c
Concentration (g/ml)
g/ml
Gram per milliliter
α
Alpha
λ
Lambda
g/L
Grams per liter


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