Fluoxetine Oral Solution

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 Oral Solution contains an amount of Fluoxetine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO). It may contain one or more preservatives.

2 IDENTIFICATION

Change to read:

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

Sample solution: Transfer a volume of Oral Solution, equivalent to 20 mg of fluoxetine, to a separatory funnel. Add 5.0 mL of water and 0.5 mL of 1 N sodium hydroxide, extract with 5 mL of chloroform, and discard the aqueous layer. Evaporate the remaining layer to dryness, and dissolve the residue in 0.4 mL of chloroform.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 Procedure

Buffer: Triethylamine and water (1:98), adjusted with phosphoric acid to a pH of 6.0

Mobile phase: Acetonitrile and Buffer (50:50)

Standard solution: 45 μg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Sample solution: Nominally 40 μg/mL of fluoxetine from Oral Solution in Mobile phase

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; packing L10

Flow rate: 1 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of

uoxetine (C₁₇H₁₈F₃NO) in the portion of Oral Solution 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 (μg/mL)

C_U = nominal concentration of fluoxetine in the Sample solution (μg/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

Deliverable Volume 〈698〉

For multiple-unit containers

Acceptance criteria: Meets the requirements

Uniformity of Dosage Units 〈905〉

For single-unit containers

Acceptance criteria: Meets the requirements

5 IMPURITIES

5.1 Organic Impurities

Solution A: 4.3 g/L of sodium 1-octanesulfonate and 13.8 g/L of monobasic sodium phosphate in water adjusted with phosphoric acid to a pH of 3.0

Solution B: Methanol, acetonitrile, and Solution A (26:21:53)

Solution C: Methanol, acetonitrile, and Solution A (22:35:43)

Mobile phase: See Table 1.

Table 1

Diluent: Methanol, acetonitrile, and Solution A (30:10:60)

Impurity identification solution: Nominally 2.0 mg/mL of USP Fluoxetine Hydrochloride RS prepared as follows. Transfer a suitable quantity of USP Fluoxetine Hydrochloride RS to a container, dissolve in 1 N sulfuric acid, and heat at 85° for 1 h.

System suitability solution: 0.1 mg/mL of USP Fluoxetine Hydrochloride RS prepared as follows. Transfer 10 mg of USP Fluoxetine Hydrochloride RS to a 100-mL volumetric flask. Add 1.0 mL of Impurity identification solution. Dissolve in and dilute with Diluent to volume.

Sample solution: Nominally 1.9 mg/mL of fluoxetine from Oral Solution in Diluent

Dilute sample solution: Nominally 76 μg/mL of fluoxetine from Sample solution in Diluent

5.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

5.3 System suitability

Sample: System suitability solution

Suitability requirements: The retention time of any peak, except the fluoxetine peak, is less than 13 min.

5.4 Analysis

Samples: Sample solution and Dilute sample solution

Calculate the percentage of each impurity in the portion of Oral Solution taken:

Result = {r_i/[r_T + (D × r_UD)]} × 100

r_i = peak response of each impurity from the Sample solution

r_T = sum of all the peak responses excluding fluoxetine from the Sample solution

D = dilution factor between the Sample solution and the Dilute sample solution, 25

r_UD = peak response of fluoxetine from the Dilute sample solution

Acceptance criteria

Any individual impurity: NMT 0.4%

Total impurities: NMT 0.8%

6 SPECIFIC TESTS

pH 〈791〉: 2.5–4.5

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Fluoxetine Hydrochloride RS