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OLANZAPINE SOP


1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of the Olanzapine 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  Yellow, crystalline 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 (96.0%).
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 and observe.
5.1.2.3.3        Add methylene chloride in test tube 2 and observe.
5.1.2.3.4        Add ethanol (96.0%) in test tube 3 and observe.
5.1.2.4  Observations:
5.1.2.4.1        The sample in test tubes 1 containing with purified water is practically insoluble.
5.1.2.4.2        The sample in test tubes 2 containing with methylene chloride is freely soluble.
5.1.2.4.3        The sample in test tube 3 containing with ethanol (96.0%) is slightly soluble.
5.2  Assay:
5.2.1        Apparatus:
5.2.1.1  HPLC apparatus.
5.2.1.2  Glassware (according to the requirement).
5.2.1.3  Magnetic stirrer.
5.2.2        Material and reagents:
5.2.2.1  50.0mg of olanzapine CRS.
5.2.2.2  1.0mg of olanzapine impurity A CRS.
5.2.2.3  Acetonitrile.
5.2.2.4  6.9g/L solution of sodium dihydrogen phosphate monohydrate.
5.2.2.5  Phosphoric acid.
5.2.2.6  12g/L of sodium dodecyl sulfate.
5.2.2.7  Purified water (q.s).
5.2.3        Requirements:
5.2.3.1  Sample:
5.2.3.1.1        50.0mg
5.2.3.2  Test solution:
5.2.3.2.1        Test solution (a):
5.2.3.2.1.1  Take 100.0ml of beaker and dissolve 50.0mg of the substance to be examined in the mobile phase.
5.2.3.2.1.2  Dilute it to 100.0ml with the mobile phase.
5.2.3.2.1.3  Take another beaker of 50.0ml and add 2.0ml of the above solution.
5.2.3.2.1.4  Dilute it with 10.0ml of the mobile phase.
5.2.3.3  Reference solutions:
5.2.3.3.1        Reference solution (a):
5.2.3.3.1.1  Take 100.0ml of beaker and dissolve 50.0mg of olanzapine CRS in the mobile phase.
5.2.3.3.1.2  Dilute it to 100.0ml with the mobile phase.
5.2.3.3.1.3  Take another beaker of 50.0ml and add 2.0ml of the above solution.
5.2.3.3.1.4  Dilute it with 10.0ml of the mobile phase.
5.2.3.3.2        Reference solution (b):
5.2.3.3.2.1  Take 100.0ml of beaker and dissolve 10.0mg of the substance to be examined and 1.0mg of olanzapine impurity A CRS in the mobile phase.
5.2.3.3.2.2  Dilute it to 100.0ml with the mobile phase.
5.2.3.4  Column:
5.2.3.4.1        Size:
5.2.3.4.1.1  Length=0.15m,
5.2.3.4.1.2  θ=4.6mm.
5.2.3.4.2        Stationary phase:
5.2.3.4.2.1  Octylsilyl silica gel for chromatography (5μm).
5.2.3.5  Mobile phase:
5.2.3.5.1        Mix 1volume of acetonitrile R with 1 volume of a 6.9g/L solution of sodium dihydrogen phosphate monohydrate R in a beaker.
5.2.3.5.2        Adjust it to a pH of 2.5 with phosphoric acid R and containing 12g/L of sodium dodecyl sulfate R.
5.2.3.6  Flow rate:
5.2.3.6.1        1.5ml/min.
5.2.3.7  Detection:
5.2.3.7.1        Spectrophotometer at 260nm.
5.2.3.8  Injection:
5.2.3.8.1        20μL.
5.2.3.9  Run time:
5.2.3.9.1        1.2times the retention time of olanzapine.
5.2.3.10    Relative retention:
5.2.3.10.1    With reference to olanzapine (retention time= about 7min): impurity A= about 0.8.
5.2.3.11    System suitability: reference solution (b):
5.2.3.11.1    Resolution: Minimum 2.0 between the peaks due to impurity A and olanzapine.
5.2.4        Method of analysis:
5.2.4.1  Firstly prepare the test solution, reference solution and mobile phase according to the requirements.
5.2.4.2  The solutions must be free from solid particles.
5.2.4.3  Prepare the apparatus, use normal procedure of liquid chromatography.
5.2.4.4  The mobile phase solvent mixtures must be deaerated prior to use either by boiling or by applying a partial vacuum to the solvent reservoir.
5.2.4.5  Equilibrate the column with the prescribed mobile phase, flow rate and at temperature specified until a suitable baseline is achieved.
5.2.4.6  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.
5.2.4.7  As the eluate leaves the column it enters a detector, where it is continuously monitored at the specified λ.
5.2.4.8  The electrical signal obtained from detector is amplified and routes to recorder which record the developed chromatogram.
5.2.4.9  Calculate the percentage content of Olanzapine (C17H20N4S) using the chromatogram obtained with the reference solution (a) and declared content of olanzapine CRS.
5.2.5        Limit:
5.2.5.1  98.0% 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 /Olanzapine: 2015, pp. 422-424.
7.2  The British Pharmacopoeia. Vol V., Official Monograph / Liquid Chromatography: 2015, Appendix: IIID pp. 202-204.
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.,

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
%
Percentage
g/L
Gram per liter
ml
Milliliter
q.s
Quantity sufficient
g
Grams
UV/VIS
Ultraviolet/ visible
ppt
Precipitate
μm
Micron
mg
Milligram
CRS
Chemical reference substance
v/v
Volume by volume
m
Meters
θ
Theta
λ
Lambda
oC
Degree centigrade
Min
Minutes
ml/min
Milliliter per minute
nm
Nanometer
μL
Microliter
B.P
British pharmacopoeia
Vol
Volume
QCA
Quality control active ingredient
F
Format


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