Fluoxetine 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

Fluoxetine Tablets contain an amount of Fluoxetine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of fluoxetine ((C₁₇H₁₈F₃NO).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: Transfer 1 Tablet to a suitable container, dissolve in 10 mL of chloroform, and pass through a suitable filter. Rinse the container with 5 mL of chloroform, and pass the rinsings through a suitable filter. Evaporate the combined filtrate in a hood with the aid of a current of air and mild heat to dryness.

Acceptance criteria: Meet the requirements

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: 7.1 g/L of sodium 1-pentane-sulfonate in water. To each L add 2.9 mL of glacial acetic acid, and adjust with 5 N sodium hydroxide solution to a pH of 5.0.

Mobile phase: Methanol and Solution A (67:33)

System suitability stock solution: 0.2 mg/mL of 4-trifluoromethylphenol in Mobile phase

System suitability solution: 0.02 mg/mL of 4-trifluoromethylphenol from System suitability stock solution and 0.11 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Standard solution: 0.1 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Sample stock solution: Transfer 10 Tablets to a 1000-mL volumetric flask. Add 500 mL of Mobile phase, and shake to disintegrate the Tablets. Dilute with Mobile phase to volume, and sonicate for 10 min.

Sample solution: Nominally 0.1 mg/mL of fluoxetine from Sample stock solution in Mobile phase. Pass through a suitable fllter. Use the flltrate.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm

Column: 4.6-mm × 7.5-cm; 3.5-μm packing L7

Column temperature: 38°

Flow rate: 1 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: System suitability solution

3.4 Suitability requirements

Resolution: NLT 4.0 between fluoxetine and 4-tri fluoromethylphenol

Tailing factor: NMT 1.7 for fluoxetine

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluoxetine ((C₁₇H₁₈F₃NO) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of fluoxetine, 309.33

M_r2 = molecular weight of fluoxetine hydrochloride, 345.79

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 1000 mL

Apparatus 1: 100 rpm

Time: 15 min

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

Sample solution: Pass 20 mL of the solution under test through a suitable filter.

Standard solution: USP Fluoxetine Hydrochloride RS in Medium having a known concentration similar to that of the Sample solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm

Column: 4.6-mm × 7.5-cm; 3.5-μm packing L7

Column temperature: 38°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 2.0 between fluoxetine and 4-trifluoromethylphenol

Tailing factor: NMT 1.7 for fluoxetine

Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) dissolved:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of fluoxetine, 309.33

M_r2 = molecular weight of fluoxetine hydrochloride, 345.79

Tolerances: NLT 80% (Q) of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Solution A: 6.5 g/L of sodium 1-octanesulfonate in water. To each L add 2.9 mL of phosphoric acid, and adjust with 5 N sodium hydroxide solution to a pH of 3.0.

Mobile phase: Acetonitrile and Solution A (43:57)

Impurity identification solution: Nominally 2.2 mg/mL of fluoxetine hydrochloride from USP Fluoxetine Hydrochloride RS prepared as follows.

Transfer 22 mg of USP Fluoxetine Hydrochloride RS to a 10-mL volumetric flask and dilute with 1 N sulfuric acid to volume. Heat the flask to 85° for 3 h, and allow to cool to room temperature. [Note - The resulting solution contains aminomethyl-1-phenylpropanol, which is also known as 3-methylamino-1-phenylpropan-1-ol or α-[2-(methylamino)ethyl]benzenemethanol.]

System suitability solution: 0.001 mg/mL of USP Fluoxetine Related Compound B RS and 0.015 mg/mL of USP Fluoxetine Hydrochloride RS prepared as follows. Transfer suitable quantities of USP Fluoxetine Related Compound B RS and USP Fluoxetine Hydrochloride RS to a 10-mL volumetric flask. Add 0.2 mL of Impurity identification solution and dilute with Mobile phase to volume.

Standard solution: 0.015 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Sensitivity solution: 0.2 μg/mL of USP Fluoxetine Hydrochloride RS from Standard solution in Mobile phase

Sample solution: 2 mg/mL of fluoxetine from Tablets prepared as follows. Transfer 10 Tablets to a suitable volumetric flask and add 50% ofthe final ask volume of Mobile phase. Shake to disintegrate and dilute with Mobile phase to volume. Sonicate the resulting solution for 10 min, pass a portion through a suitable filter, and use the filtrate.

5.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 15-cm; 3.5-μm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 3 times the retention time of fluoxetine

5.3 System suitability

Samples: Mobile phase, System suitability solution, Standard solution, and Sensitivity solution

Injection order: Mobile phase, Sensitivity solution, System suitability solution, and Standard solution

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

5.4 Suitability requirements

Resolution: NLT 4.5 between aminomethyl-1-phenylpropanol and fluoxetine related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

5.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of fluoxetine from the Standard solution

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of fluoxetine, 309.33

M_r1 = molecular weight of fluoxetine hydrochloride, 345.79

Acceptance criteria: See Table 1.

Table 1

^a 3-Methylamino-1-phenylpropan-1-ol; also known as α-[2-(Methylamino) ethyl] benzenemethanol.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Fluoxetine Hydrochloride RS

USP Fluoxetine Related Compound B RS

N-Methyl-3-phenylpropan-1-amine;

also known as N-Methyl-3-phenylpropylamine.

C₁₀H₁₅N 149.24