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= _________________
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)
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
h
Hours
Vol
Volume
QCA
Quality control active ingredient
F
Format
mV
Millivolts
v/s
Verses
Min
Minutes


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