THEOPHYLLINE METHOD OF ANALYSIS SOP


THEOPHYLLINE METHOD OF ANALYSIS SOP


1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Theophylline 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 (5 test tubes, 1 spatula, 1 pipette).
5.1.2.1.2        Ethanol (96%).
5.1.2.1.3        Mineral acids (e.g. dilute HCl, dilute H2SO4, HNO3).
5.1.2.1.4        Solutions of alkali hydroxide (e.g. NaOH, KOH).
5.1.2.1.5        Ammonia.
5.1.2.1.6        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 5 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 ethanol (96%) in test tube 2 and observe.
5.1.2.3.4        Add solution of alkali hydroxide in test tube 3 and observe.
5.1.2.3.5        Add ammonia in test tube 4 and observe.
5.1.2.3.6        Add dilute mineral acid in test tube 5 and observe.
5.1.2.4  Observations:
5.1.2.4.1        The sample in test tube 1 containing with purified water is slightly soluble.
5.1.2.4.2        The sample in test tube 2 containing with ethanol (96%) is sparingly soluble.
5.1.2.4.3        The sample in test tube 3, 4 & 5 containing with solution of alkali hydroxide, ammonia & dilute mineral acid is dissolved.
5.2  Identification tests:
5.2.1        Determination of melting point:
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (test tubes, spatula).
5.2.1.1.2        Melting point apparatus.
5.2.1.1.3        Capillary tubes.
5.2.1.2  Sample:
5.2.1.2.1        Sufficient quantity of sample.
5.2.1.3  Method:
5.2.1.3.1        Take sample dry it first in oven at 100-105oC, operate the oven according to SOP
5.2.1.3.2        Introduce the sufficient quantity of sample into a capillary tube.
5.2.1.3.3        Set the apparatus and immerse the capillary tube into the apparatus such that the closed end is near the centre of the bulb of thermometer.
5.2.1.3.4        Switch on the melting point apparatus.
5.2.1.3.5        Operate the melting point apparatus according to the SOP.
5.2.1.3.6        Raise the temperature of the apparatus.
5.2.1.3.7        Record the temperature at which the last particle passes into the liquid phase.
5.2.1.3.8        Record measurements in annexure-1.
5.2.1.4  Observations:
5.2.1.4.1        The melting point of theophylline is about 270oC to 274oC.
5.2.2         
5.2.2.1  Material and equipment:
5.2.2.1.1        Glassware (1 test tube, 1 pipette).
5.2.2.1.2        Water-bath.
5.2.2.1.3        1.0ml of 360g/L solution of potassium hydroxide.
5.2.2.1.4        1.0ml of diazotized sulfanilic acid solution.
5.2.2.2  Sample:
5.2.2.2.1        10.0mg.
5.2.2.3  Method:
5.2.2.3.1        Take a test tube and add 10.0mg of sample in it and also add 1.0ml of 360g/L solution of potassium hydroxide with the help of pipette.
5.2.2.3.2        Heat it in water bath at 90oC for 3min.
5.2.2.3.3        Then add 1.0ml of diazotized sulfanilic acid solution
5.2.2.3.4        Observe the changes.
5.2.2.3.5        Carry out the blank test too and observe its changes too.
5.2.2.4  Observations:
5.2.2.4.1        A red colour slowly develops.
5.2.3        Loss on drying:
5.2.3.1  Material and equipment:
5.2.3.1.1        Glassware (according to requirement).
5.2.3.1.2        Analytical weighing balance.
5.2.3.1.3        Oven.
5.2.3.2  Sample:
5.2.3.2.1        1.0g.
5.2.3.3  Method:
5.2.3.3.1        Weigh 1.0g of the test sample.
5.2.3.3.2        Set the oven apparatus. Operate it according to the SOP.
5.2.3.3.3        Place the sample into the tray and dry it.
5.2.3.3.4        Set the temperature of oven at 105oC for at least 45min.
5.2.3.3.5        And wait till the sample loses its moisture.
5.2.3.3.6        After 45min weigh the sample again by using analytical weighing balance i.e. the final weight.
5.2.3.3.7        Note down readings on given Annexure-2.
5.2.3.4  Observation:
5.2.3.4.1        Maximum 0.5%.
5.2.4        Xanthine test:
5.2.4.1  Material and equipment:
5.2.4.1.1        Glassware (1 test tube, 1 pipette).
5.2.4.1.2        0.1ml of strong hydrogen peroxide solution.
5.2.4.1.3        0.3ml of dilute hydrochloric acid.
5.2.4.1.4        0.1ml of dilute ammonia R2.
5.2.4.1.5        Water-bath.
5.2.4.2  Sample:
5.2.4.2.1        A few milligrams of ppt obtained from point 5.2.1.
5.2.4.3  Method:
5.2.4.3.1        Take a test tube and add few milligrams of ppt in it.
5.2.4.3.2        Add 0.1ml of strong hydrogen peroxide solution and 0.3ml of dilute hydrochloric acid.
5.2.4.3.3        Heat it on water-bath until it completely dry and yellowish-red residue is obtained.
5.2.4.3.4        Add 0.1ml of dilute ammonia R2.
5.2.4.3.5        Observe the changes.
5.2.4.4  Observations:
5.2.4.4.1        The colour of the residue changes to violet-red.
5.3  Assay:
5.3.1        Apparatus:
5.3.1.1  Glassware (according to requirement).
5.3.1.2  Titration apparatus.
5.3.1.3  Magnetic stirrer.
5.3.2        Material and reagents:
5.3.2.1  20.0ml of 0.1M silver nitrate.
5.3.2.2  1.0ml of bromothymol blue solution R1 (as indicator).
5.3.2.3  0.1M sodium hydroxide.
5.3.2.4  Purified water.
5.3.3        Sample:
5.3.3.1  0.150g.
5.3.4        Method of analysis:
5.3.4.1  Sample titration:
5.3.4.1.1        Take a flask and add in it 0.150g of sample.
5.3.4.1.2        Dissolve it in 100.0ml of purified water by using magnetic stirrer i.e. SOP.
5.3.4.1.3        Add 20.0ml of 0.1M silver nitrate and shake.
5.3.4.1.4        Use 1.0ml of bromothymol blue solution R1 as indicator.
5.3.4.1.5        Set titration apparatus.
5.3.4.1.6        Titrate with 0.1M sodium hydroxide, until colour is changed.
5.3.4.1.7        Note down the volume used as shown in Annexure-3.
5.3.4.1.8        Take at least 3 readings and take average of it.
5.3.4.2  Blank titration:
5.3.4.2.1        Take a flask and add in it 100.0ml of purified water and add 20.0ml of 0.1M silver nitrate and shake.
5.3.4.2.2        Use 1.0ml of bromothymol blue solution R1 as indicator.
5.3.4.2.3        Set titration apparatus.
5.3.4.2.4        Titrate with 0.1M sodium hydroxide, until colour is changed.
5.3.4.2.5        Note down the volume used as shown in Annexure-3.
5.3.4.2.6        Take at least 3 readings and take average of it.
5.3.4.3  Calculate percentage purity.
5.3.4.4  Calculations:
5.3.4.4.1        After taking average volume of both blank titration and sample titration. Calculate the volume used by the examined substance by using formula:
Volume used by substance = Blank titration - Sample titration.
5.3.4.4.2        For percentage purity use formula:
%age purity = volume used by substance x factor x 100
                                                                                         Weight of sample
5.3.4.4.3        Put values and calculate %age purity.
5.3.5        Factor:
5.3.5.1  1ml of 0.1M sodium hydroxide is equivalent to 18.02mg of theophylline C7H8N4O2.
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 II., Official Monograph /Theophylline: 2015, pp. 1010-1011.
7.2  The British Pharmacopoeia. Vol V., Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0  ANNEXURES:
Annexure 1: Observations of Melting point apparatus.
Annexure 2: Observations of Percentage Loss of drying by using oven.
Annexure 3: Observations and calculations of assay.





Annexure: 1
Observations of Melting point apparatus
Melting point apparatus
Sample = _____________
Time period = _____________
Sr.#
Initial (Ti)
(oC)
Final (Tf)
(oC)
Tf - Ti
(oC)












Average: _____________











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
Observations and calculations of assay
Indicator: ___________________
Weight of sample: ____________                                                Factor: _____________
Titrant: _____________________
Sample titration
Sr.#
Initial volume (vi)
(ml)
Final volume (vf)
(ml)
vf-vi
(ml)
1.



2.



3.



Average volume: _________________
Blank titration
Sr.#
Initial volume (vi)
(ml)
Final volume (vf)
(ml)
vf-vi
(ml)
1.



2.



3.



Average volume: _________________
Calculations:
Volume used by substance = Blank titration – Sample titration.

%age purity = volume used by substance x factor x 100
                                                                     Weight of sample



Result: ____________________________________________________________________
9.0  ABBREVIATIONS:
Abbreviation
Expanded Form
SOP
Standard operating procedure
&
And
No.
Number  
Ltd.
Limited
QCA
Quality control active ingredient
F
Format
Q.C
Quality control
Vol
Volume
BP
British Pharmacopoeia
g
Grams
ml
Milliliter
h
Hours
Min
Minutes
ppt
Precipitates
oC
Degree centigrade
mg
Milligram
M
Molar
vi
Initial volume
vf
Final volume
%
Percentage
g/L
Grams per liter
R
Reagent
Ti
Initial temperature
Tf
Final temperature
Temp.
Temperature



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