Fluvoxamine Maleate Tablets: Official July 1, 2009

Revision Bulletin
Official July 1, 2009
Fluvoxamine 1
TEST 1
Fluvoxamine Maleate Tablets

Fluvoxamine Maleate Tablets contain not less than
90.0 percent and not more than 110.0 percent of the labeled amount of fluvoxamine maleate (C15H21F3N2O2
C4H4O4).
Packaging and storagePreserve in tight containers. Store at
room temperature.
LabelingIf a test for Related compounds other than Test 1 is
used, then the labeling states with which Related compounds test
the article complies.
USP Reference standards 11USP Fluvoxamine Maleate RS.
IdentificationThe retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: water; 900 mL, degassed.
Apparatus 2: 50 rpm.
Time: 30 minutes.
ProcedureDetermine the amount of C15H21F3N2O2 C4H4O4
dissolved by employing UV absorption at the wavelength of maximum absorbance at about 246 nm on portions of the solution passed
through a suitable 0.45-m filter, suitably diluted with Medium, if
necessary, in comparison with a Standard solution having a known
concentration of USP Fluvoxamine Maleate RS in the same Medium. When there are known interferences due to excipients, excipient interference corrections may be applied, as necessary.
TolerancesNot less than 80% (Q) of the labeled amount of
C15H21F3N2O2 C4H4O4 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Change to read:
Related compounds[NOTEIf (E)-5-methoxy-4-difluoromethylvalerophenone-O-2-aminoethyloxime is a known impurity,
Test 2 is recommended.]
Buffer solution, Mobile phase, Resolution solution, and

Chromatographic systemProceed as directed in the Assay.
Identification solutionDissolve a quantity of maleic acid in Mobile phase, and dilute quantitatively, and stepwise if necessary, with
Mobile phase to obtain a solution having a concentration of about
0.35 mg per mL.
Standard solutionUse the Standard preparation, prepared as
directed in the Assay.
Test solutionUse the Assay stock preparation, prepared as directed in the Assay.
ProcedureSeparately inject equal volumes (about 20 L) of the
Standard solution, the Test solution, and the Identification solution
into the chromatograph, record the chromatograms, and measure the
responses for the major peaks. Calculate the percentage of impurities in the portion of Tablets taken by the formula:
100(C/D)F(ri / rS)
in which C is the concentration, in mg per mL, of USP Fluvoxamine Maleate RS in the Standard solution; D is the expected concentration, in mg per mL, of fluvoxamine maleate taking into account the labeled amount and the amount of sample taken to
prepare the Test solution; F is the response factor of each impurity
as given in Table 1; ri is the individual peak area of each impurity
in the Test solution; and rS is the peak area of fluvoxamine maleate
in the Standard solution. The limits of impurities are specified in
Table 1. [NOTEDisregard any peak due to maleic acid or to the
reagent blank.]
TEST 2
DiluentPrepare a mixture of methanol and water (60 : 40).
Acetate bufferDissolve about 13.6 g of sodium acetate trihydrate in 1000 mL of water.
Mobile phasePrepare a filtered and degassed mixture of Acetate buffer, acetonitrile, and methanol (550 : 300 : 150). Add 2 mL
of triethylamine. Adjust with glacial acetic acid to a pH of 4.5.
Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solutionQuantitatively dilute the Standard preparation, prepared as directed in the Assay, with Diluent to obtain a final
Table 1
Compound Name
Maleic acid
5-Methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(E)-O[2-[(2-succinyl)amino]ethyl]oxime
5-Methoxy-4-(trifluoromethyl)valerophenone(E)-O-(2aminoethyl)aminoethyl oxime maleate
Z-isomer
Fluvoxamine
4-(Trifluoromethyl)valerophenone(E)-O-2-(2aminoethyl)aminoethyl oxime maleate
(E)-O-2-(2-Aminoethyl)-4-(trifluoromethyl)--phenylacetophenone oxime maleate
4-(Trifluoromethyl)valerophenone(E)-O-(2-aminoethyl)oxime
maleate
5-Methoxy-4-(trifluoromethyl)valerophenone oxime
5-Methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(E)-O(2-aminoethyl] oxime maleic acid monoamide
5-Methoxy-4-(trifluoromethyl)valerophenone ketone
Unknown impurities
Total
Relative
Retention Time
about 0.19
about 0.50
Response Factor
1.0
Limit %
0.8
about 0.67
1.4
0.2
about 0.79
1.0
about 1.18
1.0
1.0
0.5
0.2
about 1.74
1.0
0.2
about 2.00
1.0
0.2
about 3.45
about 4.3
0.6
1.0
0.2
0.2
about 4.2
0.3
1.0
0.2
0.1
1.8
2009 The United States Pharmacopeial Convention
All Rights Reserved.
Revision Bulletin
Official July 1, 2009
Fluvoxamine
solution having a known concentration of about 0.001 mg per mL

of fluvoxamaine maleate.
Test solutionTransfer 5 mL of the Assay stock preparation (the
supernatant after centrifugation), prepared as directed in the Assay,
to a 50-mL volumetric flask, and dilute with Diluent to volume.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 4.6mm 25-cm column that contains packing L7. The flow rate is
about 2.0 mL per minute. The column temperature is maintained at
40. Chromatograph 20 L of the Resolution solution, and record
the peak responses as directed for Procedure. Identify the peaks using the relative retention times given in Table 2; the resolution, R,
between the Z-isomer and fluvoxamine maleate is not less than 1.0.
Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more
than 2.0; and the relative standard deviation for replicate injections
is not more than 5.0%.
ProcedureSeparately inject equal volumes (about 100 L) of
the Standard solution and the Test solution into the chromatograph,
record the chromatograms, and measure the responses for all the
impurities and fluvoxamine maleate. Calculate the percentage of
impurities in the portion of Tablets taken by the formula:
100(C/D)(1/F)(ri / rS)
in which C is the concentration, in mg per mL, of USP Fluvoxamine Maleate RS in the Standard solution; D is the expected concentration, in mg per mL, of fluvoxamine maleate taking into account the labeled amount and the amount of sample taken to
prepare the Test solution; F is the response factor of each impurity
as given in Table 2; ri is the individual peak area of each impurity
in the Test solution; and rS is the peak area of fluvoxamine maleate
in the Standard solution. The limits of impurities are specified in
Table 2.
Assay
Buffer solutionDissolve approximately 5 g of 1-pentanesulfonic acid sodium salt and 0.7 g of monobasic potassium phosphate in 620 mL of water. Adjust with phosphoric acid to a pH of
3.00 0.05.
Mobile phasePrepare a filtered and degassed mixture of Buffer
solution and acetonitrile (62 : 38). Make adjustments if necessary
(see System Suitability under Chromatography 621).
Resolution solutionTransfer approximately 6 mg of fluvoxamine maleate to a 50-mL volumetric flask. Heat the sample at
120 for 10 minutes. Cool to room temperature, and add 3.0 mL of
0.1 N hydrochloric acid. Heat the solution in a water bath for 10
minutes. Cool to room temperature, add 50 mg of fluvoxamine
Compound Name
(E)-5-methoxy-4-difluoromethylvalerophenone-O-2aminoethyloxime
(E)-N-[2[[[-(4-methoxybutyl)-4-(trifluoromethyl)benzylidene]
amino]oxy]ethyl]aspartic acid
(E)-5-methoxy-4-trifluoromethylvalerophenone-O-[2-N(aminoethyl)aminoethyl]oxime
Z-isomer
Fluvoxamine
(E)-4-trifluoromethyl-valerophenone-O-2-aminoethyloxime
5-Methoxy-4-trifluoromethylvalerophenone oxime
5-Methoxy-4-trifluoromethylvalerophenone
Unknown impurities
Total
maleate, and dissolve in 25 mL of Mobile phase. Dilute with Mobile phase to volume, and mix.
Standard preparationDissolve an accurately weighed quantity
of USP Fluvoxamine Maleate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a
solution having a known concentration of about 0.05 mg per mL.
Assay stock preparationWeigh and finely powder not fewer
than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 500 mg of fluvoxamine maleate, to a 500mL volumetric flask, add about 250 mL of Mobile phase, sonicate
for about 15 minutes, shake by mechanical means for about 15 minutes, dilute with Mobile phase to volume, and mix. Centrifuge a
portion of this solution for 10 minutes.
Assay preparationTransfer 5.0 mL of the supernatant from the
Assay stock preparation to a 100-mL volumetric flask and dilute to
volume with Mobile phase. Pass a portion of this solution through a
filter having a 45-m or finer porosity, and use the filtrate.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 234-nm detector and a 4.6mm 25-cm column that contains packing L7. The flow rate is
about 1.7 mL per minute. The column temperature is maintained at
40. Chromatograph the Resolution solution, and record the peak
responses as directed for Procedure: the relative retention times are
about 0.19 for maleic acid, 0.5 for 5-methoxy-1-[4(trifluoromethyl)phenyl]-1-pentanone-(E)-O-[2-[(2-succinyl)amino]ethyl]oxime, 0.79 for the Z-isomer, and 1.0 for fluvoxamine
maleate; and the resolution, R, between the Z-isomer and fluvoxamine maleate is not less than 2.0 and not less than 5.0 between 5methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(E)-O-[2-[(2succinyl)amino]ethyl]oxime and the Z-isomer. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the column efficiency is not less than 5000 theoretical
plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
ProcedureSeparately inject equal volumes (about 20 L) of the
Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses
for the fluvoxamine maleate peaks. Calculate the quantity, in mg, of
fluvoxamine maleate (C15H21F3N2O2 C4H4O4) in the portion of
Tablets taken by the formula:
10,000C(rU / rS)
in which C is the concentration, in mg per mL, of USP Fluvoxamine Maleate RS in the Standard preparation; and rU and rS are
the peak areas obtained from the Assay preparation and the Standard preparation, respectively.
Table 2
Approx. Relative
Retention Time
0.58
Response Factor
1.0
Limit %
0.2
1.2
0.70
1.0
0.75
1.0
0.2
0.85
1.0
1.86
about 1.99
about 2.17
0.5
1.0
1.0
1.0
1.0
0.5
0.2
0.2
0.2
0.2
1.5
2009 The United States Pharmacopeial Convention
All Rights Reserved.
(RB 1-Jul-2009)

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Revision Bulletin

Official July 1, 2009

Fluvoxamine Maleate Tablets

Buffer solution, Mobile phase, Resolution solution, and

2009 The United States Pharmacopeial Convention

All Rights Reserved.

solution having a known concentration of about 0.001 mg per mL

2009 The United States Pharmacopeial Convention

All Rights Reserved.

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