ITRACONAZOLE
SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Itraconazole 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 (3 test
tubes, spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
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 3 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, Methylene chloride in test tube 2 and Ethanol (96%) 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 containing with purified water is practically insoluble.
5.1.2.4.2
The sample in test
tube 2 containing with Methylene chloride is freely soluble.
5.1.2.4.3
The sample in test
tube 3 containing with Ethanol (96%) is very 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 4 hours.
5.2.3.5
And wait till the sample
loses its moisture.
5.2.3.6
After 4 hours 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
Apparatus:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Potentiometer.
5.3.1.3
Magnetic stirrer.
5.3.2
Material
and reagents:
5.3.2.1
Anhydrous acetic
acid.
5.3.2.2
Methyl ethyl
ketone.
5.3.2.3
0.1M Perchloric
acid.
5.3.2.4
Crystal violet
solution.
5.3.3
Sample:
5.3.3.1
0.300g.
5.3.4
Method
of analysis:
5.3.4.1 Take
a 100.0ml of beaker and take 0.300g of sample in it.
5.3.4.2 Add
70.0ml of a mixture of 1 volume anhydrous acetic acid and 7 volumes of methyl
ethyl ketone in it and dissolve it by using magnetic stirrer for 10 minutes.
5.3.4.3 Fill
the right hand side burette with titrant 0.1M Perchloric acid.
5.3.4.4 Carry
out a Potentiometric titration using crystal violet solution as an indicator.
5.3.4.5 Operate
potentiometer according to SOP.
5.3.4.6 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.
5.3.4.7 Plot
a graph, volume used v/s millivolts.
5.3.4.8 Find
out the END POINT, potentiometrically at the second point of inflexion.
5.3.4.9 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.3.4.10 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.3.4.11 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.3.4.12 Calculate
percentage purity of the sample by using formula:
%age
purity = volume used by substance x factor x 100
Weight of sample
5.3.5
Factor:
5.3.5.1 1ml
of 0.1M Perchloric acid is equivalent to 35.3mg of Itraconazole C35H38Cl2N8O4.
5.3.6
Limit:
5.3.6.1
99.0% 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 /Itraconazole: 2015, pp. 1276-1277.
8.0 ANNEXURES:
Annexure 1: Observations
of Percentage Loss of drying by using oven.
Annexure 2: Assay
observations and calculations (Potentiometric titration).
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=
_________________
Average % Loss of Moisture: _____________
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
|
|
Q.C
|
Quality
control
|
|
B.P
|
British
pharmacopoeia
|
|
M
|
Molar
|
|
g
|
Grams
|
|
ml
|
Milliliter
|
|
mg
|
Milligram
|
|
%
|
Percentage
|
|
h
|
Hours
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
mV
|
Millivolts
|
|
v/s
|
Verses
|
|
Min
|
Minutes
|