Fluvoxamine Maleate Tablets
DEFINITION
Fluvoxamine Maleate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fluvoxamine maleate (C15H21F3N2O2·C4H4O4).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
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:
Acetonitrile and Buffer (19:31)
System suitability solution:
6 mg of fluvoxamine maleate to a 50-mL volumetric flask. Heat the sample at 120
for 10 min. 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 min. 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.
for 10 min. 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 min. 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.
Standard solution:
0.05 mg/mL of USP Fluvoxamine Maleate RS in Mobile phase
Sample stock solution:
Transfer a weighed quantity of finely powdered Tablets from NLT 20 Tablets to a suitable volumetric flask to obtain a nominal concentration of 1 mg/mL of fluvoxamine maleate. Add 50% of flask volume of Mobile phase. Sonicate for 15 min followed by mechanical shaking for 15 min. Dilute with Mobile phase to volume. Centrifuge a portion of this solution for 10 min.
Sample solution:
0.05 mg/mL from Sample stock solution diluted with Mobile phase. [Note—Pass a portion of this solution through a filter with a 0.45-µm or finer pore size, and use the filtrate. ]
Chromatographic system
Mode:
LC
Detector:
UV 234 nm
Column:
4.6-mm × 25-cm; packing L7
Column temperature:
40
Flow rate:
1.7 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for maleic acid, 5-methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(E)-O-[2-[(2-succinyl)amino]ethyl]oxime, Z-isomer, and fluvoxamine maleate are 0.19, 0.5, 0.79, 1.0, respectively, System suitability solution. ]
Suitability requirements
Resolution:
NLT 2.0 between the Z-isomer and fluvoxamine maleate; NLT 5.0 between 5-methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(E)-O-[2-[(2-succinyl)amino]ethyl]oxime and the Z-isomer, System suitability solution
Column efficiency:
NLT 5000 theoretical plates, Standard solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C15H21F3N2O2·C4H4O4 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| CS | = | = concentration of USP Fluvoxamine Maleate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of fluvoxamine maleate in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
Water; 900 mL, degassed
Apparatus 2:
50 rpm
Time:
30 min
Standard solution:
USP Fluvoxamine Maleate RS at a known concentration in Medium
Sample solution:
Centrifuge portions of the solution under test at 2000 rpm for 10 min, and dilute with Medium, if necessary.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
246 nm
Analysis
Samples:
Standard solution and Sample solution
When there are known interferences due to excipients, excipient interference corrections may be applied, as necessary.
Tolerances:
NLT 80% (Q) of the labeled amount of C15H21F3N2O2·C4H4O4 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
[Note—If (E)-5-methoxy-4¢-difluoromethylvalerophenone-O-2-aminoethyloxime is a known impurity, Test 2 is recommended. ]
Test 1
Buffer, Mobile phase, System suitability solution, Standard solution, and Chromatographic system:
Proceed as directed in the Assay.
Identification solution:
0.35 mg/mL of maleic acid in Mobile phase
Sample solution:
Use the Sample stock solution, prepared as directed in the Assay.
Analysis
Samples:
Identification solution, Standard solution, and Sample solution
[Note—Disregard any peak due to maleic acid or the reagent blank. ]
Calculate the percentage of impurities in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × F × 100
| rU | = | = individual peak area of each impurity from the Sample solution |
| rS | = | = peak area of fluvoxamine maleate from the Standard solution |
| CS | = | = concentration of USP Fluvoxamine Maleate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of fluvoxamine maleate from the Sample solution (mg/mL) |
| F | = | = response factor of each impurity as given in Impurity Table 1 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.8%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Maleic acid | 0.19 | — | — |
| 5-Methoxy-1-[4-(trifluoromethyl) phenyl]-1-pentanone-(E)-O-[2-[(2-succinyl)amino] ethyl]oxime |
0.50 | 1.0 | 0.8 |
| 5-Methoxy-4¢-(trifluoromethyl) valerophenone(E)-O-(2-aminoethyl) aminoethyl oxime maleate |
0.67 | 1.4 | 0.2 |
| Z-isomer | 0.79 | 1.0 | 0.5 |
| Fluvoxamine | 1.0 | — | — |
| 4¢-(Trifluoro methyl)valerophenone(E)-O-2-(2-aminoethyl)aminoethyl oxime maleate |
1.18 | 1.0 | 0.2 |
(E)-O-2-(2-Aminoethyl)-4-(trifluoromethyl)- -phenyl-acetophenoneoxime maleate |
1.74 | 1.0 | 0.2 |
| 4¢-(Trifluoro methyl)valerophenone(E)-O-(2-aminoethyl) oxime maleate |
2.00 | 1.0 | 0.2 |
| 5-Methoxy-4¢-(trifluoromethyl) valerophenone oxime |
3.45 | 0.6 | 0.2 |
| 5-Methoxy-1-[4-(trifluoromethyl) phenyl]-1-pentanone-(E)-O-(2-aminoethyl]oxime maleic acid monoamide |
4.3 | 1.0 | 0.2 |
| 5-Methoxy-4¢-(trifluoromethyl) valerophenone ketone |
4.2 | 0.3 | 0.2 |
| Unknown impurities | — | 1.0 | 0.1 |
Test 2
Diluent:
Methanol and water (3:2)
Solution A:
13.6 mg/mL of sodium acetate trihydrate in water
Mobile phase:
Acetonitrile, methanol, and Solution A (6:3:11). Add 2 mL of triethylamine. Adjust with glacial acetic acid to a pH of 4.5.
System suitability solution:
Proceed as directed in the Assay.
Standard solution:
0.001 mg/mL of fluvoxamine maleate in Diluent prepared by dilution of the Standard solution in the Assay
Sample stock solution:
Prepare as directed in the Assay.
Sample solution:
0.1 mg/mL of fluvoxamine maleate from Sample stock solution and Diluent
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; packing L7
Column temperature:
40
Flow rate:
2 mL/min
Injection size:
100 µL; 20 µL for the System suitability solution
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 1.0 between the Z-isomer and fluvoxamine maleate, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Measure the responses for all the impurities and fluvoxamine maleate. Calculate the percentage of impurities in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = individual peak area of each impurity from the Sample solution |
| rS | = | = peak area of fluvoxamine maleate from the Standard solution |
| CS | = | = concentration of USP Fluvoxamine Maleate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of fluvoxamine maleate in the Sample solution (mg/mL) |
| F | = | = relative response factor of each impurity as given in Impurity Table 2 |
Acceptance criteria
Individual impurities:
See Impurity Table 2.
Total impurities:
NMT 1.5%
Impurity Table 2
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| (E)-5-methoxy-4¢-difluoromethyl valerophenone-O-2-amino ethyloxime |
0.58 | 1.0 | 0.2 |
| (E)-N-[2[[[-(4-methoxybutyl)-4-(trifluoromethyl) benzylidene]amino] oxy]ethyl]aspartic acid |
0.70 | 1.0 | 1.2 |
| (E)-5-methoxy-4¢-trifluoromethyl valerophenone-O-[2-N-(aminoethyl) aminoethyl]oxime |
0.75 | 1.0 | 0.2 |
| Z-isomer | 0.85 | 0.5 | 0.5 |
| Fluvoxamine | 1.0 | — | — |
| (E)-4¢-trifluoromethylvalerophenone-O-2-aminoethyloxime | 1.86 | 1.0 | 0.2 |
| 5-Methoxy-4¢-trifluoromethyl valerophenone oxime |
1.99 | 1.0 | 0.2 |
| 5-Methoxy-4-trifluoromethyl valerophenone |
2.17 | 1.0 | 0.2 |
| Unknown impurities | — | 1.0 | 0.2 |
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at room temperature.
• Labeling:
If a test in Procedure under Organic Impurities other than Test 1 is used, then the labeling states with which test the article complies.
• USP Reference Standards 11
11
USP Fluvoxamine Maleate RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3273
Pharmacopeial Forum: Volume No. 32(6) Page 1684