Fluvoxamine Maleate

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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C₁₅H₂₁F₃N₂O₂·C₄H₄O₄ 434.41

1-Pentanone, 5-methoxy-1-[4-(trifluoromethyl)phenyl]-, O-(2-aminoethyl)oxime, (E)-, (Z)-2-butenedioate (1:1);

(E)-5-Methoxy-4'-(trifluoromethyl)valerophenone O-(2-aminoethyl)oxime, maleate (1:1) CAS RN^®: 61718-82-9; UNII: 5LGN83G74V.

1 DEFINITION

Fluvoxamine Maleate contains NLT 98.0% and NMT 102.0% of fluvoxamine maleate (C₁₅H₂₁F₃N₂O₂·C₄H₄O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

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

3 ASSAY

3.1 PROCEDURE

Solution A: 8 g/L of sodium 1-pentanesulfonate and 1.1 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 solution: 0.05 mg/mL of Fluvoxamine Maleate in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 234 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 of fluvoxamine

3.2 System suitability

Samples: System suitability solution and Standard solution

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

Suitability requirements

Resolution: NLT 3.0 between the 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

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluvoxamine maleate (C₁₅H₂₁F₃N₂O₂·C₄H₄O₄) in the portion of Fluvoxamine Maleate 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 = concentration of Fluvoxamine Maleate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

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

Identification solution: 0.35 mg/mL of maleic acid in Mobile phase

Sample solution: 1 mg/mL of Fluvoxamine Maleate in Mobile phase

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 impurity in the portion of Fluvoxamine Maleate taken:

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

r_U = peak area of each impurity 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 = concentration of Fluvoxamine Maleate in the Sample solution (mg/mL)

F = relative response factor for each impurity (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 impurities.

^b (E)-5-Methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone 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.

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry under vacuum at 80° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed, light-resistant containers. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Fluvoxamine Maleate RS