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:
Average: _______________
Optical
rotation of blank solution: _______________
Sample solution:
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=
_________________
Average
% 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:
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
|
%
|
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
|