TERBINAFINE HYDROCHLORIDE METHOD
OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Terbinafine
hydrochloride 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 (4 test
tubes, spatula).
5.1.2.1.2
Anhydrous ethanol.
5.1.2.1.3
Methanol.
5.1.2.1.4
Acetone.
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, anhydrous ethanol in test tube 2, methanol in test tube 3, acetone
in test tube 4 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 very slightly or slightly soluble.
5.1.2.4.2
The sample in test
tube 2 and 3 containing with anhydrous ethanol is freely soluble.
5.1.2.4.3
The sample in test
tube 4 containing with acetone is slightly soluble.
5.2 Identification
test:
5.2.1
Chlorides
test:
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Anhydrous ethanol.
5.2.1.1.3
Dilute nitric
acid.
5.2.1.1.4
Purified water
(q.s).
5.2.1.1.5
0.4ml of Silver
nitrate R1.
5.2.1.1.6
1.5ml of ammonia.
5.2.1.2
Sample:
5.2.1.2.1
Quantity of
substance to be examined equivalent to about 2.0mg of chloride.
5.2.1.3
Method:
5.2.1.3.1
Take a test tube
add in it 2.0ml of anhydrous ethanol with the help of pipette.
5.2.1.3.2
Dissolve in 2.0ml
of anhydrous ethanol a quantity of the substance to be equivalent to about
2.0mg of chloride.
5.2.1.3.3
Acidify with
dilute nitric acid.
5.2.1.3.4
And add 0.4ml of
silver nitrate R1.
5.2.1.3.5
Shake and allow it
to stand.
5.2.1.3.6
A curdled, white
ppt is formed.
5.2.1.3.7
Centrifuge it in
centrifugation machine, according to SOP No. BM/QCEO/SOP010-00.
5.2.1.3.8
The obtained ppt
is wash with 3 quantities, each of 1ml, of water.
5.2.1.3.9
Carry out this
operation rapidly is subdued light, degrading the fact that the supernatant
solution may not become perfectly clear.
5.2.1.3.10 Suspend
the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.2.1.4
Observations:
5.2.1.4.1
The precipitate
dissolves easily with the possible exception of a few large particles which
dissolves slowly.
5.3 Loss
on drying:
5.3.1
Material and equipment:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Analytical
weighing balance.
5.3.1.3
Oven.
5.3.2
Sample:
5.3.2.1
1.0g.
5.3.3
Method:
5.3.3.1
Weigh 1.0g of the
test sample.
5.3.3.2 Set
the oven apparatus. Operate it according to the SOP
5.3.3.3
Place the sample
into the tray and dry it.
5.3.3.4
Set the
temperature of oven at 105oC for at least 45 minutes.
5.3.3.5
And wait till the
sample loses its moisture.
5.3.3.6
After 45 minutes
weigh the sample again by using analytical weighing balance i.e. the final
weight.
5.3.3.7
Note down readings
on given Annexure-1.
5.3.4
Observation:
5.3.4.1
Maximum 0.5%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Potentiometer.
5.4.2
Material
and reagents:
5.4.2.1
50.0ml of ethanol
(96%).
5.4.2.2
5.0ml of 0.01M hydrochloric
acid.
5.4.2.3
0.1M sodium
hydroxide.
5.4.2.4
Thymolphthalein solution.
5.4.3
Sample:
5.4.3.1
0.250g.
5.4.4
Method
of analysis:
5.4.4.1 Take
a 100.0ml of beaker and take 0.250g of sample in it.
5.4.4.2 Add
50.0ml of ethanol (96%). Dissolve it by using magnetic stirrer i.e. SOP
5.4.4.3 Add
5.0ml of 0.01M hydrochloric acid, dissolve it again.
5.4.4.4 Fill
the right hand side burette with titrant 0.1M sodium hydroxide.
5.4.4.5 Carry
out a Potentiometric titration using thymolphthalein solution as an indicator.
5.4.4.6 Operate
potentiometer according to SOP.
5.4.4.7 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.
5.4.4.8 Plot
a graph, volume used v/s millivolts.
5.4.4.9 Find
out the END POINT.
5.4.4.10 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.4.4.11 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.4.4.12 Calculate
volume used by substance by using formula:
Volume used by
substance = Blank titration - Sample titration.
5.4.4.13 Calculate
percentage purity of the sample by using formula:
%age purity = volume
used by substance x factor x 100
Weight of sample
5.4.5
Factor:
5.4.5.1 1ml
of 0.1M sodium hydroxide is equivalent to 32.79mg of Terbinafine hydrochloride
C21H26ClN.
5.4.6
Limit:
5.4.6.1
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 II.,
Official Monograph /Terbinafine hydrochloride: 2015, pp. 987-988.
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
|
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