GABAPENTIN SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Gabapentin 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 (5 test
tubes, 1 spatula).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
Dilute acids (e.g.
dil. HCl, dil. H2SO4).
5.1.2.1.5
Dilute alkali
hydroxide (e.g. dil. NaOH).
5.1.2.1.6
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 5 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 Ethanol (96%) in
test tube 2 and observe.
5.1.2.3.4
Add methylene
chloride in test tube 3 and observe.
5.1.2.3.5
Add dil. HCl in
test tube 4 and observe.
5.1.2.3.6
Add dil. NaOH in
test tube 5 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 containing with purified water is sparingly soluble.
5.1.2.4.2
The sample in test
tube 2 containing with Ethanol (96%) is slightly soluble.
5.1.2.4.3
The sample in test
tube 3 containing with methylene chloride is practically insoluble.
5.1.2.4.4
The sample in test
tube 4 and 5 containing with dil. HCl & dil. NaOH is dissolved. (7.1)
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
Monobasic ammonium
phosphate.
5.2.2.2
Phosphoric acid.
5.2.2.3
Sodium
perchlorate.
5.2.2.4
Perchloric acid.
5.2.2.5
Acetonitrile.
5.2.2.6
Purified water.
5.2.3
Sample:
5.2.3.1
14.0mg.
5.2.4
Diluent:
5.2.4.1
2.32g/L of
monobasic ammonium phosphate in purified water. Adjust with phosphoric acid to
a pH of 2.0.
5.2.5
Buffer:
5.2.5.1
0.58g/L of
monobasic ammonium phosphate and 1.83g/L of sodium perchlorate in purified
water. Adjust with Perchloric acid to a pH of 1.8.
5.2.6
Mobile
phase:
5.2.6.1
Acetonitrile and
buffer (24:76).
5.2.7
Standard
solution:
5.2.7.1
14.0mg/ml of USP
Gabapentin RS in diluent.
5.2.8
System
suitability solution:
5.2.8.1
2.3mg/ml of USP
gabapentin RS from the standard solution in diluent.
5.2.9
Sample
solutions:
5.2.9.1
14.0mg/ml of
Gabapentin in diluent.
5.2.10
Chromatographic
system:
5.2.10.1
Mode:
Liquid chromatography.
5.2.10.2
Detector:
UV
215nm.
5.2.10.3
Column:
4.6mm
x 25cm; packing L1.
5.2.10.4
Temperature:
40o.
5.2.10.5
Flow
rate: 1.0ml/min.
5.2.10.6
Injection
volume: 20μL.
5.2.11 System suitability:
5.2.11.1
Samples:
Standard
solution and system suitability solution.
5.2.11.2
Suitability
requirements:
5.2.11.2.1 Column efficiency:
NLT
1900 theoretical plates for the gabapentin peak, system suitability solution.
5.2.11.2.2 Relative standard
deviation: NMT 2.0% for the gabapentin peak, standard
solution.
5.2.12 Analysis:
5.2.12.1
Samples:
Standard
solution and sample solution.
5.2.13 Procedure:
5.2.13.1
Equilibrate the
column and detector with mobile phase at specified flow rate until a constant
signal is received.
5.2.13.2
Separately inject
equal volumes (about 20μl) of the standard solution and the sample solution
into the chromatogram.
5.2.13.3
Record the
spectrum.
5.2.13.4
And measure the
responses for the analyte peaks.
5.2.13.5
Calculate the percentage
of gabapentin (C19H17NO2) in the portion of
gabapentin taken:
Result
= (rU/rS) x (CS/CU) x 100.
rU
= peak area from the sample solution.
rS
= peak area from the standard solution.
CS
= concentration of USP gabapentin RS in the standard solution (mg/ml).
CU
= concentration of gabapentin in the sample solution (mg/ml).
5.2.14 Acceptance
criteria:
5.2.14.1 98.0%
to 102.0% on anhydrous basis. (7.2)
6.0 REVISION LOG:
Revision No.
|
Effective Date
|
Reason
|
00
|
|
New SOP
|
7.0 REFERENCES:
7.1
The British
Pharmacopoeia. Vol I.,
Official Monograph / Gabapentin: 2015, pp. 1053-1054.
7.2 USP38NF33
Volume-4 Official Monograph/Gabapentin: 2015, pp.: 3630-3631.
7.3
USP38NF33
Volume-1 Official Monograph/ Chromatography: 2015, pp.: 424-434.
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:
________________________________________________________________________________________________________________________________________________
|
9.0 ABBREVIATIONS:
Abbreviation
|
Expanded Form
|
SOP
|
Standard
operating procedure
|
&
|
And
|
No.
|
Number
|
Ltd.
|
Limited
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|
Q.C
|
Quality
control
|
Vol
|
Volume
|
g
|
Grams
|
ml
|
Milliliter
|
oC
|
Degree
centigrade
|
mg
|
Milligram
|
M
|
Molar
|
%
|
Percentage
|
R
|
Reagent
|
μm
|
Micron/
micrometer
|
g/L
|
Gram
per liter
|
CRS
|
Chemical
reference solution
|
m
|
Meter
|
θ
|
Theta
|
mm
|
Millimeter
|
ml/min
|
Milliliter
per minute
|
nm
|
Nanometer
|
μL
|
Microliter
|
Min
|
Minute
|
λ
|
Lamda
|
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