Maleic acid
Transfer about 800.0 mg of Fluvoxamine Maleate, accurately weighed, to a 250-mL conical flask containing 50 mL of water. Titrate with 0.1 N sodium hydroxide VS, using 0.5 mL of phenolphthalein TS as the indicator. Perform a blank determination, and make any necessary correction (see
Titrimetry 541). Each mL of 0.1 N sodium hydroxide VS is equivalent to 5.805 mg of maleic acid (C
4H
4O
4). Between 26.0% and 27.5% of maleic acid is found.
Related compounds
Buffer solution, Mobile phase, Resolution solution, and Chromatographic system
Proceed as directed in the Assay.
Identification solution
Dissolve a quantity of maleic acid in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.35 mg per mL.
Standard solution
Use the Standard preparation, prepared as directed in the Assay.
Test solution
Use the Assay stock preparation, prepared as directed in the Assay.
Procedure
Separately inject equal volumes (about 20 µL) 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 Fluvoxamine Maleate taken by the formula:
5000(C/W)F(ri / rS),
in which
C is the concentration, in mg per mL, of
USP Fluvoxamine Maleate RS in the
Standard solution; W is the weight, in mg, of Fluvoxamine Maleate used 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 the reagent blank.
]
Table 1
Compound Name |
Relative Retention Time |
Response Factor |
Limit (%) |
Maleic acid |
about 0.19 |
|
|
5-Methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-
(E)-O-[2-[(2-succinyl)amino]ethyl]oxime |
about 0.50 |
1.0 |
0.3 |
5-Methoxy-4¢-(trifluoromethyl)valerophenone(E)-O-
(2-aminoethyl)aminoethyl oxime maleate |
about 0.67 |
1.4 |
0.2 |
Z-isomer |
about 0.79 |
1.0 |
0.5 |
Fluvoxamine |
1.0 |
|
|
4¢-(Trifluoromethyl)valerophenone(E)-O-2-(2-aminoethyl)aminoethyl oxime maleate |
about 1.18 |
1.0 |
0.2 |
(E)-O-2-(2-Aminoethyl)-4-(trifluoromethyl)--phenyl-
acetophenone oxime maleate |
about 1.74 |
1.0 |
0.2 |
4¢-(Trifluoromethyl)valerophenone(E)-O-(2-aminoethyl)
oxime maleate |
about 2.00 |
1.0 |
0.2 |
5-Methoxy-4¢-(trifluoromethyl)valerophenone oxime |
about 3.45 |
0.6 |
0.2 |
5-Methoxy-4¢-(trifluoromethyl)valerophenone ketone |
about 4.2 |
0.3 |
0.2 |
Unknown impurities |
|
1.0 |
0.1 |
Total |
|
|
1.5 |
Assay
Buffer solution
Dissolve about 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 phase
Prepare a filtered and degassed mixture of
Buffer solution and acetonitrile (62:38). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Resolution solution
Transfer about 6 mg of Fluvoxamine Maleate to a 50-mL volumetric flask. Heat the sample at 120
for 10 minutes. Cool down 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 down to room temperature, add 50 mg of Fluvoxamine Maleate, and dissolve in 25 mL of
Mobile phase. Dilute with
Mobile phase to volume, and mix.
Standard preparation
Dissolve 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 preparation
Transfer an accurately weighed quantity of about 50 mg of Fluvoxamine Maleate to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Assay preparation
Transfer 5.0 mL of the Assay stock preparation to a 100-mL volumetric flask. Dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 234-nm detector and a 4.6-mm × 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 0.2 for maleic acid, 0.5 for 5-methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(
E)-
O-[2-[(2-succinyl)amino]ethyl]oxime, 0.8 for the
Z-isomer, and 1.0 for fluvoxamine maleate; the resolution,
R, between the
Z-isomer and fluvoxamine maleate is not less than 3.0 and not less than 5.0 between 5-methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(
E)-
O-[2-[(2-succinyl)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%.
Procedure
Separately inject equal volumes (about 20 µL) 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 C
15H
21F
3N
2O
2 · C
4H
4O
4 in the portion of Fluvoxamine Maleate taken by the formula:
1000C(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.