Fluvoxamine Maleate Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Fluvoxamine Maleate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fluvoxamine maleate (C₁₅H₂₁F₃N₂O₂·C₄H₄O₄).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

3.1 PROCEDURE

Solution A: 8 g/L of 1-pentanesulfonic acid sodium salt and 1.1 (ERR 1-May-2023) g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.00 ± 0.05.

Mobile phase: Acetonitrile and Solution A (38:62)

System suitability solution: Transfer 6 mg of fluvoxamine maleate to a 50-mL volumetric flask. Heat the sample at 120° for 10 min. Cool 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 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: Nominally 1 mg/mL of fluvoxamine maleate from Tablets prepared as follows. Finely powder NLT 20 Tablets and transfer a portion of the powder to a suitable volumetric flask. Add 50% of the 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: Nominally 0.05 mg/mL from Sample stock solution diluted with Mobile phase. Pass through a filter of 0.45-µm or finer pore size.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 234 nm. For Identification B, use a diode array detector in the range of 210-400 nm.

Column: 4.6-mm × 25-cm; 5-µm packing L7

Column temperature: 40°

Flow rate: 1.7 mL/min

Injection volume: 20 µL

Run time: NLT 2.5 times the retention time of fluvoxamine

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between Z-isomer and fluvoxamine maleate; NLT 5.0 between succinyl fluvoxamine and the Z-isomer, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluvoxamine maleate (C₁₅H₂₁F₃N₂O₂·C₄H₄O₄) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

C_S = concentration of USP Fluvoxamine Maleate RS in the Standard solution (mg/mL)

C_U = nominal concentration of fluvoxamine maleate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: Water; 900 mL, degassed

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: USP Fluvoxamine Maleate RS in Medium

Sample solution: Centrifuge a portion of the solution under test, and dilute with Medium, if necessary. [NOTE-The use of a centrifuge speed of NLT 2000 rpm for NLT 10 min may be suitable.]

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

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.

Calculate the percentage of the labeled amount of fluvoxamine maleate (C₁₅H₂₁F₃N₂O₂·C₄H₄O₄) dissolved:

Result = (A_U/A_S) x C_S x D x V x (1/L) × 100

A_U= absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

D = dilution factor for the Sample solution, if needed

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fluvoxamine maleate (C₁₅H₂₁F₃N₂O₂·C₄H₄O₄) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES, PROCEDURE 1

Use Procedure 1 when the impurity profile includes aminoethyl desmethoxy fluvoxamine, dealkyl benzyl fluvoxamine, or fluvoxamine maleamide.

Solution A, Mobile phase, System suitability solution, Standard solution, and System suitability: Proceed as directed in the Assay.

Sample solution: Use the Sample stock solution, prepared as directed in the Assay.

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 6 times the retention of fluvoxamine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak area of each degradation product from the Sample solution

r_S = peak area of fluvoxamine from the Standard solution

C_S = concentration of USP Fluvoxamine Maleate RS in the Standard solution (mg/mL)

C_U = nominal concentration of fluvoxamine maleate in the Sample solution (mg/mL)

F = relative response factor for each degradation product (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a This is the counterion. It is not to be reported or included in the total degradation products for the drug product.

^b 5-Methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone (E)-O-[2-[(2-succinyl)amino]ethyl]oxime.

^c (E)-5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one-O-{2-[(2-aminoethyl)amino]ethyl} oxime.

^d (Z)-5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one-O-(2-aminoethyl)oxime.

^e (E)-1-[4-(Trifluoromethyl)phenyl]pentan-1-one O-{2-[(2-aminoethyl)amino]ethyl} oxime.

^f (E)-2-Phenyl-1-[4-(trifluoromethyl)phenyl]ethan-1-one O-(2-aminoethyl) oxime.

^g (E)-1-[4-(Trifluoromethyl)phenyl] pentan-1-one O-(2-aminoethyl) oxime.

^h (E)-5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one oxime.

ⁱ 5-Methoxy-1-(4-(trifluoromethyl)phenyl)pentan-1-one.

^j (22,9E)-4-Oxo-10-[4-(trifluoromethyl)phenyl]-8,15-dioxa-5,9-diazahexadeca-2,9-dienoic acid.

5.2 ORGANIC IMPURITIES, PROCEDURE 2

Use Organic Impurities, Procedure 2 when the impurity profile includes desfluoro fluvoxamine.

Solution A: 13.6 g/L of sodium acetate in water

Mobile phase: Acetonitrile, methanol, and Solution A (30:15:55). To each L add 2 mL of triethylamine, and adjust with glacial acetic acid to a pH of 4.5.

Diluent: Methanol and water (60:40)

System suitability solution: Prepare 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: Nominally 0.1 mg/mL of fluvoxamine maleate from Sample stock solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm;

5-µm packing L7

Column temperature: 40°

Flow rate: 2 mL/min

Injection volumes

System suitability solution: 20 μL

Other solutions: 100 µL

Run time: NLT 2.5 times the retention time of fluvoxamine

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.0 between Z-isomer and fluvoxamine, 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

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) × 100

r_U = peak area of each degradation product from the Sample solution

r_S = peak area of fluvoxamine from the Standard solution

C_S = concentration of USP Fluvoxamine Maleate RS in the Standard solution (mg/mL)

C_U = nominal concentration of fluvoxamine maleate in the Sample solution (mg/mL)

F = relative response factor for each impurity (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a (E)-1-[4-(Difluoromethyl)phenyl]-5-methoxypentan-1-one O-(2-aminoethyl) oxime.

^b 5-Methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone (E)-O-[2-[(2-succinyl)amino]ethyl]oxime.

^c (E)-5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one-O-{2-[(2-aminoethyl)amino]ethyl} oxime.

^d (Z)-5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one O-(2-aminoethyl) oxime.

^e (E)-1-[4-(Trifluoromethyl)phenyl]pentan-1-one O-(2-aminoethyl) oxime.

^f (E)-5-Methoxy-1-[4-(trifluoromethyl)phenyl] pentan-1-one oxime.

^g 5-Methoxy-1-(4-(trifluoromethyl)phenyl)pentan-1-one.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store at controlled room temperature.

6.2 LABELING

The labeling indicates which test for Organic Impurities is used only if Procedure 1 is not used.

6.3 USP REFERENCE STANDARDS (11)

USP Fluvoxamine Maleate RS