ESOMEPRAZOLE
MAGNESIUM TRIHYDRATE SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Esomeprazole magnesium trihydrate
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 slightly
colored powder.
5.1.1.2
Slightly
hygroscopic.
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
Methanol.
5.1.2.1.3
Heptane.
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, Methanol in test tube 2 and Heptane in test tube 3 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 soluble.
5.1.2.4.3
The sample in test
tube 3 containing with acetone is practically insoluble.
5.2 Assay:
5.2.1
Apparatus:
5.2.1.1
HPLC apparatus.
5.2.1.2
Glassware
(according to the requirement).
5.2.2
Material
and reagents:
5.2.2.1
11.0ml of a
95.0g/L solution of trisodium phosphate dodecahydrate.
5.2.2.2
22.0ml of a
179.1g/L solution of disodium hydrogen phosphate.
5.2.2.3
10.0ml of
methanol.
5.2.2.4
10.0mg of
omeprazole CRS.
5.2.2.5
Acetonitrile.
5.2.2.6
1.4g/L solution of
disodium hydrogen phosphate R.
5.2.2.7
phosphoric acid R.
5.2.2.8
Purified water.
5.2.3
Sample:
5.2.3.1
10.0mg.
5.2.4
Buffer
solution pH 11.0:
5.2.4.1
Take a beaker of
100.0ml and add 11.0ml of a 95.0g/L solution of trisodium phosphate
dodecahydrate R and 22.0ml of a 179.1g/L solution of disodium hydrogen
phosphate R.
5.2.4.2
Mix it by using
magnetic stirrer operate according to SOP.
5.2.4.3
And then dilute it
to 100.0ml with purified water.
5.2.5
Test
solution:
5.2.5.1
Take a beaker of
500.0ml and add 10.0mg of the substance to be examined with the help of spatula
in about 10.0ml of methanol.
5.2.5.2
Dissolve it by using
magnetic stirrer operate according to SOP.
5.2.5.3
Add 10.0ml of
buffer solution pH 11.0.
5.2.5.4
Dilute it to
200.0ml with purified water.
5.2.6
Reference
solutions:
5.2.6.1
Take a beaker of
500.0ml and add 10.0mg of omeprazole CRS with the help of spatula in about
10.0ml of methanol.
5.2.6.2
Dissolve it by using
magnetic stirrer operate according to SOP.
5.2.6.3
Add 10.0ml of
buffer solution pH 11.0.
5.2.6.4
Dilute it to
200.0ml with purified water.
5.2.7
Column:
5.2.7.1
Size:
5.2.7.1.1
Length=0.125m,
5.2.7.1.2
θ=4mm.
5.2.7.2
Stationary
phase:
5.2.7.2.1
Octylsilyl silica
gel for chromatography R (5μm).
5.2.8
Mobile
phase:
5.2.8.1
Mix 3 5 volumes of acetonitrile and 65 volumes of a
1.4g/L solution of disodium hydrogen phosphate R previously adjusted to a pH
7.6 with phosphoric acid R.
5.2.9
Flow
rate:
5.2.9.1
1.0ml/min.
5.2.10
Detection:
5.2.10.1 Spectrophotometer
at 280nm.
5.2.11
Injection:
5.2.11.1 20μL.
5.2.12 Run time:
5.2.12.1 1.5
times the retention time of esomeprazole.
5.2.13 Retention time:
5.2.13.1 Esomeprazole=about
4 min.
5.2.14 Method of
analysis:
5.2.14.1 Firstly
prepare the test solution, reference solution and mobile phase according to the
requirements.
5.2.14.2 The
solutions must be free from solid particles.
5.2.14.3 Prepare
the apparatus.
5.2.14.4 The
mobile phase solvent mixtures must be de-aerated prior to use either by boiling
or by applying a partial vacuum to the solvent reservoir.
5.2.14.5 Equilibrate
the column with the prescribed mobile phase, flow rate and at temperature
specified until a suitable baseline is achieved.
5.2.14.6 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.
5.2.14.7 As
the eluate leaves the column it enters a detector, where it is continuously
monitored at the specified λ.
5.2.14.8 The
electrical signal obtained from detector is amplified and routes to recorder
which record the developed chromatogram.
5.2.14.9 Calculate
the percentage content of Esomeprazole (C34H36MgN6O6S2)
from the declared content of omeprazole CRS.
5.2.15
Factor:
5.2.15.1 1.0g
of omeprazole is equivalent to 1.032g of esomeprazole magnesium.
5.2.16 Observations:
5.2.16.1 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 I.,
Official Monograph / Esomeprazole
magnesium trihydrate: 2015, pp. 879-881.
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
spectrum.
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
|
|
B.P
|
British
pharmacopoeia
|
|
Vol
|
Volume
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
μm
|
Micron/
micrometer
|
|
g/L
|
Gram
per liter
|
|
ml
|
Milliliter
|
|
mg
|
Milligram
|
|
CRS
|
Chemical
reference solution
|
|
m
|
Meter
|
|
θ
|
Theta
|
|
mm
|
Millimeter
|
|
oC
|
Degree
Celsius
|
|
ml/min
|
Milliliter
per minute
|
|
nm
|
Nanometer
|
|
μL
|
Microliter
|
|
Min
|
Minute
|
|
λ
|
Lamda
|
|
%
|
Percentage
|