DULOXETINE
HYDROCHLORIDE SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of Duloxetine Hydrochloride USP 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 Identification
test:
5.1.1
Chloride
test:
5.1.1.1
Material and equipment:
5.1.1.1.1
Glassware
(according to requirement).
5.1.1.1.2
Dilute nitric
acid.
5.1.1.1.3
Purified water.
5.1.1.1.4
0.5ml of Silver
nitrate solution.
5.1.1.1.5
Ammonia.
5.1.1.2
Sample:
5.1.1.2.1
5mg/ml in
methanol.
5.1.1.3
Method:
5.1.1.3.1
Take a test tube
prepare in it 5mg/ml in methanol TS.
5.1.1.3.2
Add one drop of
diluted nitric acid.
5.1.1.3.3
And add 0.5ml of
silver nitrate TS.
5.1.1.3.4
Shake and allow it
to stand.
5.1.1.3.5
A curdled, white
ppt is formed.
5.1.1.3.6
Centrifuge the
mixture without delay in centrifugation machine, operate it according to SOP
No. BM/QCEO/SOP010-00.
5.1.1.3.7
Decant the
supernatant layer.
5.1.1.3.8
Wash the obtained
ppt with three 1.0ml of portions of nitric acid solution (1 in 100), and
discard the washing.
5.1.1.3.9
Add ammonia TS
drop-wise to this ppt.
5.1.1.3.10 Observe
the changes.
5.1.1.4
Observations:
5.1.1.4.1
The precipitate
dissolves readily.
5.2 Assay:
5.2.1
Apparatus:
5.2.1.1
Liquid
chromatography apparatus.
5.2.1.2
Analytical
weighing balance.
5.2.1.3
Glassware
(according to the requirement).
5.2.1.4
Magnetic stirrer.
5.2.1.5
UV/VIS
Spectrophotometer.
5.2.2
Material
and reagents:
5.2.2.1
Phosphoric acid.
5.2.2.2
Sodium hydroxide
solution.
5.2.2.3
10.3g of sodium
1-hexanesulfonate monohydrate.
5.2.2.4
n-propanol.
5.2.2.5
Acetonitrile.
5.2.2.6
Purified water.
5.2.2.7
USP Duloxetine
hydrochloride RS.
5.2.3
Requirements:
5.2.3.1
Buffer:
5.2.3.1.1
Take a beaker of
1000.ml with purified water.
5.2.3.1.2
Add 2.9g of
phosphoric acid in it, dissolve it by using magnetic stirrer operate according
to SOP No. BM/QCEO/SOP007-00.
5.2.3.1.3
Adjust with sodium
hydroxide solution to a pH of 2.5.
5.2.3.1.4
To each L of this
solution add 10.3g of sodium 1-hexanesulfonate monohydrate, and dissolve by
using magnetic stirrer.
5.2.3.2
Mobile
phase:
5.2.3.2.1
Acetonitrile,
n-propanol and buffer (13:17:70).
5.2.3.3
Diluent:
5.2.3.3.1
Acetonitrile and
purified water (25:75).
5.2.3.4
System
suitability solution:
5.2.3.4.1
0.2mg/ml of USP
Duloxetine hydrochloride RS in mobile phase. Heat the solution to at least 40o
for a minimum of 1h.
[NOTE___The
resulting solution contains Duloxetine impurity B, Duloxetine impurity C,
Duloxetine impurity D, Duloxetine impurity E and Duloxetine related compound
F.]
5.2.3.5
Standard
solution:
5.2.3.5.1
0.1mg/ml of USP
Duloxetine hydrochloride RS in diluent.
5.2.3.6
Sample
solution:
5.2.3.6.1
0.1mg/ml of
Duloxetine hydrochloride in diluent.
5.2.3.7
Chromatographic
system:
5.2.3.7.1
Mode:
Liquid chromatography.
5.2.3.7.2
Detector:
UV
230nm.
5.2.3.7.3
Column:
4.6mm
x 15cm; 3.5μm packing L7.
5.2.3.7.4
Column
temperature: 40±3o.
5.2.3.7.5
Flow
rate: 1.0ml/min.
5.2.3.7.6
Injection
size: 10μL.
5.2.3.7.7
Run
time: 2 times the retention time of Duloxetine.
5.2.3.8 System
suitability:
5.2.3.8.1
Sample:
System
suitability solution.
[NOTE___
see table in Annexure-1 for relative retention times.]
5.2.3.8.2
Suitability
requirements:
5.2.3.8.2.1 Resolution: NLT
1.5 between Duloxetine and Duloxetine related compound F peaks.
5.2.3.8.2.2 Tailing factor: NMT
1.5, for the Duloxetine peak.
5.2.3.8.2.3 Relative standard
deviation: NMT 1.0%, for the Duloxetine peak.
5.2.3.9 Analysis:
5.2.3.9.1
Samples:
5.2.3.9.1.1 Standard
solution and sample solution.
5.2.3.9.2
Calculate the
percentage of Duloxetine hydrochloride (C18H19NOS.HCl) in
the portion of sample taken:
Result= (rU/rS) x (CS/CU)
x 100.
rU=
peak response from the sample solution.
rS=
peak response from the standard solution.
CS=
concentration of USP Duloxetine hydrochloride RS in the standard solution
(mg/mL).
CU=
concentration of Duloxetine hydrochloride in the sample solution (mg/mL).
5.2.3.9.3
Acceptance
criteria:
5.2.3.9.3.1 97.0%-102.0%
on the dried basis.
5.2.4
Procedure:
5.2.4.1 Protect
the solution of Duloxetine from light.
5.2.4.2 Equilibrate
the column and detector with mobile phase at specified flow rate until a
constant signal is received.
5.2.4.3 Inject
a sample and standard solution of 10μl through the injector, or use an
auto-sampler.
5.2.4.4 Begin
the gradient program.
5.2.4.5 Record
the spectrum.
5.2.4.6 Analyze
as directed in the monograph.
6.0 REVISION LOG:
|
Revision No.
|
Effective Date
|
Reason
|
|
00
|
|
New SOP
|
7.0 REFERENCES:
7.1 USP38NF33
Volume-4 Official Monograph/ Duloxetine hydrochloride: 2015, pp.: 3243-3244.
8.0 ANNEXURES:
Annexure 1: Table
for Relative retention time.
Annexure 2: Observations
and calculations of HPLC method.
Annexure:
1
Table
for Relative retention time
|
Name
|
Relative retention time
|
Related response factor
|
Acceptance criteria NMT (%)
|
|
Duloxetine impurity Ba,g
|
0.15
|
0.36
|
-
|
|
Duloxetine impurity
Cb,g
|
0.43
|
1.0
|
-
|
|
Duloxetine impurity Dc,g
|
0.48
|
1.8
|
-
|
|
Duloxetine impurity Ed,g
|
0.74
|
1.0
|
-
|
|
Duloxetine
|
1.0
|
-
|
-
|
|
Duloxetine related compound Fe
|
1.1
|
1.0
|
0.5
|
|
Duloxetine impurity Gi,g
|
1.4
|
0.51
|
-
|
|
Any individual unspecified impurity
|
-
|
1.0
|
0.1
|
|
Total impurities
|
-
|
-
|
0.6
|
a 3-(Methylamino)-1-(thiophen-2-yl)
propan-1-ol.
b
4-[3-(
Methylamino)-1-(thiophen-2-yl) propyl] naphthalen-1-ol.
c
Naphthalen-1-ol.
d
1-(3-(Methylamino)-1-(thiophen-2-yl) proply) naphthalen-2-ol.
e
(S)-N-Methly-3-(naphthalen-1-yloxy)-3-(thiophen.3-yl) propan-1-amine.
f
1-
Fluoronaphthalene.
g
controlled at Any individual unspecified
impurity level.
Annexure:
2
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
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
Q.C
|
Quality
control
|
|
ml
|
Milliliter
|
|
ppt
|
Precipitate
|
|
L
|
Length
|
|
g/L
|
Gram
per liter
|
|
mg/ml
|
Milligram
per milliliter
|
|
μg/ml
|
Microgram
per milliliter
|
|
UV/VIS
|
Ultra
violet/ Visible
|
|
μg
|
Microgram
|
|
mg
|
Milligram
|
|
RS
|
Reference
standard
|
|
UV
|
Ultra
violet
|
|
USP
|
United
states pharmacopoeia
|
|
nm
|
Nanometer
|
|
mm
|
Millimeter
|
|
cm
|
Centimeter
|
|
μm
|
Micron
|
|
oC
|
Degree
centigrade
|
|
ml/min.
|
Milliliter
per minute
|
|
μL
|
Microliter
|
|
NMT
|
Not
more than
|
|
%
|
Percentage
|
|
NF
|
National
formulary
|
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