ESOMEPRAZOLE MAGNESIUM TRIHYDRATE SOP



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: ___________________
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 spectrum.






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
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


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