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.
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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: ___________________
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)=
_____________
2.
Retention volume:
Flow rate= _______________ml/min.
3.
Retention factor:
Retention time of unretained peak (tm)=
_____________
4.
Separation factor (α):
5.
Resolution:
Retention time of unretained peak (tm)=
_____________
6.
Efficiency:
7.
Height equivalent to a theoretical plate (HETP):
Length of column = ________________________
8.
Symmetry factor (tailing factor):
9.
Response factor & Relative response factor:
Conc. (mg/ml)= ___________________
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:
________________________________________________________________________________________________________________________________________________
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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
|