PAROXETINE HYDROCHLORIDE HEMIHYDRATE


1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of Paroxetine hydrochloride hemihydrate 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, spatula).
5.1.2.1.2        Purified water.
5.1.2.1.3        Methylene chloride.
5.1.2.1.4        Ethanol 96%.
5.1.2.1.5        Methanol.
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, methanol in test tube 2, ethanol (96%) in test tube 3 and methylene chloride in test tube 4 separately 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 slightly soluble.
5.1.2.4.2        The sample in test tube 2 containing with methanol is freely soluble.
5.1.2.4.3        The sample in test tube 3 and 4 containing with ethanol (96%) and methylene chloride is sparingly soluble.
5.2  Identification test:
5.2.1         
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (according to requirement).
5.2.1.1.2         
5.2.1.2  Sample:
5.2.1.2.1        A quantity of the substance to be examined equivalent to about 15mg of chloride.
5.2.1.3  Method:
5.2.1.3.1        Take a test tube add in it a quantity of the substance to be examined equivalent to about 15mg of chloride.
5.2.1.3.2        Add 0.2g of potassium dichromate and 1.0ml of sulfuric acid.
5.2.1.3.3        Place a filter paper strip impregnated with 0.1ml of diphenylcarbazide solution over the opening of the test tube.
5.2.1.3.4        Observe the changes.
5.2.1.3.5        Contact the impregnated paper with the potassium dichromate.
5.2.1.4  Observations:
5.2.1.4.1        Paper turns violet-red.
5.2.1.4.2        The impregnated paper must not come into contact with the potassium dichromate.
5.3  Assay:
5.3.1        Apparatus:
5.3.1.1  HPLC apparatus.
5.3.1.2  Glassware (according to the requirement).
5.3.2        Material and reagents:
5.3.2.1  50.0mg Paroxetine hydrochloride hemihydrate CRS.
5.3.2.2  5.0mg of Paroxetine impurity A CRS.
5.3.3        Requirements:
5.3.3.1  Sample:
5.3.3.1.1        50.0mg (sample to be examined).
5.3.3.2  Test solution:
5.3.3.2.1        Take 100ml of beaker and dissolve 50.0mg of the substance to be examined in sufficient quantity of purified water.
5.3.3.2.2        And dilute to 100.0ml with the same solvent.
5.3.3.3  Reference solutions:
5.3.3.3.1        Reference solution (a):
5.3.3.3.1.1  Take 100ml beaker and dissolve 50.0mg Paroxetine hydrochloride hemihydrate CRS in sufficient quantity of purified water.
5.3.3.3.1.2  And dilute to 100.0ml with the same solvent.
5.3.3.3.2        Reference solution (b):
5.3.3.3.2.1  Take 50ml beaker and dissolve 50.0mg Paroxetine hydrochloride hemihydrate CRS and 5.0mg of Paroxetine impurity A CRS in sufficient quantity of purified water.
5.3.3.3.2.2  And dilute to 10.0ml with the same solvent.
5.3.3.4  Column:
5.3.3.4.1        Size:
5.3.3.4.1.1  Length=0.25m,
5.3.3.4.1.2  θ=4.6mm.
5.3.3.4.2        Stationary phase:
5.3.3.4.2.1  Trimethylsilyl silica gel for chromatography (5μm).
5.3.3.5  Mobile phase:
5.3.3.5.1        Take a beaker of 1000.0ml and add 3.85g of ammonium acetate R in purified water R.
5.3.3.5.2        Adjust to pH 5.5 with anhydrous acetic acid R.
5.3.3.5.3        Dilute it to 600.0ml with the same solvent.
5.3.3.5.4        Add 400.0ml of acetonitrile.
5.3.3.5.5        Add 10.0ml of triethylamine slowly with stirring.
5.3.3.5.6        Readjust to the pH 5.5 with anhydrous acetic acid.
5.3.3.6  Flow rate:
5.3.3.6.1        1.0ml/min.
5.3.3.7  Detection:
5.3.3.7.1        Spectrophotometer at 295nm.
5.3.3.8  Injection:
5.3.3.8.1        10μL.
5.3.3.9  Run time:
5.3.3.9.1        Twice the retention time of Paroxetine.
5.3.4        System suitability:
5.3.4.1  Reference solution (b):
5.3.4.1.1        Resolution: Minimum 2 between the peaks due to Paroxetine and impurity A.
5.3.5        Method of analysis:
5.3.5.1  Firstly prepare the test solution, reference solution and mobile phase according to the requirements.
5.3.5.2  The solutions must be free from solid particles.
5.3.5.3  Prepare the apparatus.
5.3.5.4  The mobile phase solvent mixtures must be deaerated prior to use either by boiling or by applying a partial vacuum to the solvent reservoir.
5.3.5.5  Equilibrate the column with the prescribed mobile phase, flow rate and at temperature specified until a suitable baseline is achieved.
5.3.5.6  Test solution of the mixture to be separated is now introduced into the mobile phase with the help of an injector just before entering the separating column.
5.3.5.7  As the eluate leaves the column it enters a detector, where it is continuously monitored at the specified λ.
5.3.5.8  The electrical signal obtained from detector is amplified and routes to recorder which record the developed chromatogram.
5.3.5.9  Calculate the percentage content of Paroxetine hydrochloride using the chromatogram obtained with reference solution (a).
5.3.6        Limit:
5.3.6.1  97.5% to 102.0% (anhydrous 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 /Paroxetine hydrochloride hemihydrate: 2015, pp. 507-509.
8.0  ANNEXURES:
Annexure 1: Observations and calculations of HPLC method.




Annexure: 1
Observations and calculations of HPLC method
Analysis on HPLC
Instrument: ___________________                                           Date: _________________
Model: ___________________           
Column size:
Length=
θ=
Stationary phase:

Temperature:

Mobile phase:

Flow rate:

Injection size:

Detector:

Wavelength:
λ=

Sample solution: _______________________
Reference standard solution: ______________
Impurities: ____________________________
(calculate each component calculation separately)
OBSERVATIONS:
Attach chromatogram.






CALCULATIONS:
1.      Retention time:                                                                                n= no. of peak
Retention time of unretained peak (tm)= _____________
No. of peaks
Retention time of peak of interest
(tr)n
Height of peak of interest
(h)n
Width of peak of interest
(w)n
Area of peak of interest
A=1/2(h x w)




















2.      Retention volume:
Flow rate= _______________ml/min.
No. of peaks
Retention time of peak of interest
(tr)n
Retention volume = retention time x flow rate












3.      Retention factor:
Retention time of unretained peak (tm)= _____________
No. of peaks
Retention time of peak of interest
(tr)n
Retention factor of a component
k= (tr-tm)/tm













4.      Separation factor (α):
No. of peaks
Retention factor of a component
(kn)
Relative retention of two adjacent peaks
α = k2/k1












5.      Resolution:
Retention time of unretained peak (tm)= _____________
No. of peaks
Retention time of peak of interest
(tr)n
Width of peak of interest
(w)n
Resolution
Rs = 2 (tr2-tr1)
        (w1-w2)
















6.      Efficiency:
No. of peaks or components
Retention time of peak of interest
(tr)n
Width of peak of interest
(w)n
Efficiency
(No. of theoretical plates)
N= 16 (tr/w)2


















7.      Height equivalent to a theoretical plate (HETP):
Length of column = ________________________
No. of peaks or components
No. of theoretical plates
(N)
Height equivalent to a theoretical plate HETP = L/N












8.      Symmetry factor (tailing factor):
No. of peaks or components
Distance from the peak max. to leading edge of the peak
(f)
Width w
Symmetry factor
At 5%
At 10%
As = w5%
       2f
As = w10%
       2f
























9.      Response factor & Relative response factor:
Conc. (mg/ml)= ___________________
No. of peak
Peak area
Response factor = (peak area/conc.)
Relative response factor = (response factor of impurity/response factor of API)

















10.  Relative standard deviation (%RSD):
Use formula of relative standard deviation where it is required i.e.,
https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcSaQVcHe6gxvev49TCGtnMo64gnQ-6-Ilt9DWxADmbQyzxMgA8UFg
11.  Percentage of content:
Percentage content = (rU/rS) x (CS/CU) x 100.
rU= peak response of substance from the sample solution.
rS= peak response of substance from the standard solution.
CS= concentration of substance in the standard solution (mg/mL).
CU= concentration of substance in the sample solution (mg/mL).











RESULTS:
________________________________________________________________________________________________________________________________________________


9.0  ABBREVIATIONS:
Abbreviation
Expanded Form
SOP
Standard operating procedure
&
And
No.
Number  
Ltd.
Limited
Q.C
Quality control
UV/VIS
Ultraviolet/ visible
Mg
Milligram
Approx.
Approximately
Mm
Millimeter
cm
Centimeter
Μm
Micron/ micrometer
%
Percentage
mg
Milligram
g
Grams
w/v
Weight by volume
ml
Milliliter
Min
Minute
λ
Lambda
nm
Nanometer
μL
Microliter
oC
Degree Celsius
BPCRS
British pharmacopoeia chemical reference substance
B.P
British pharmacopoeia
Vol
Volume
F
Format
QCf
Quality control finished product test


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