Fluoxetine Hydrochloride

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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C₁₇H₁₈F₃NO · HCl 345.79

Benzenepropanamine, N-methyl-γ-[4-(trifluoromethyl)phenoxy]-, hydrochloride, (±);

(±)-N-Methyl-3-phenyl-3-[(α,α,α-trifluoro-p-tolyl)oxy]propylamine, hydrochloride;

N-Methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine hydrochloride CAS RN®: 56296-78-7; UNII: I9W7N6B1KJ.

1 DEFINITION

Fluoxetine Hydrochloride contains NLT 98.0% and NMT 102.0% of fluoxetine hydrochloride (C₁₇H₁₈F₃NO · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

B. Identification Tests - General 〈191〉, Chemical Identification Tests, Chloride: Meets the requirements

Add the following:

C. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP1-Dec-2019)

3 ASSAY

Change to read:

3.1 Procedure

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

Mobile phase: Stabilizer-free tetrahydrofuran, methanol, and Buffer (30:10:60)

Standard solution: 0.11 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Sample solution: 0.11 mg/mL of Fluoxetine Hydrochloride in Mobile phase

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm

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

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 1.2 times the retention time of fluoxetine (USP 1-Dec-2019)

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73% (USP 1-Dec-2019)

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of

uoxetine hydrochloride (C₁₇H₁₈F₃NO · HCl) in the portion of Fluoxetine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 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 = concentration of Fluoxetine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Change to read:

4.1 Organic Impurities

Buffer and Mobile phase: Prepare as directed in the Assay.

System suitability solution: Dissolve about 22 mg of USP Fluoxetine Hydrochloride RS in 10 mL of 1 N sulfuric acid VS . (USP 1-Dec-2019)

Heat at 85° for 3 h. Cool, and transfer 0.4 mL of this solution to a 25-mL volumetric flask. Add 28 mg of USP Fluoxetine Hydrochloride RS, 1mg of USP Fluoxetine Related Compound A RS, and 1 mg of USP Fluoxetine Related Compound B RS. Dilute with Mobile phase to volume.

Sensitivity solution: 0.0028 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase (USP 1-Dec-2019)

Sample solution A: 5.6 mg/mL of Fluoxetine Hydrochloride in Mobile phase

Sample solution B: 1.1 mg/mL of Fluoxetine Hydrochloride from Sample solution A in Mobile phase

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

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

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of fluoxetine

4.3 System suitability

Samples: System suitability solution and Sensitivity solution (USP 1-Dec-2019)

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

4.4 Suitability requirements

Resolution: NMT 1.1 for the ratio of the height of the fluoxetine related compound A peak to the depth of the valley between the fluoxetine and fluoxetine related compound A peaks (measured from the fluoxetine related compound A peak height), System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Dec-2019)

4.5 Analysis

Samples: Sample solution A and Sample solution B

Calculate the percentage of fluoxetine related compound A in the portion of Fluoxetine Hydrochloride taken:

Result = [r_iB /(r_iB + r_UB )] × 100

r_iA = peak response of fluoxetine related compound A from Sample solution B

r_UB = peak response of fluoxetine from Sample solution B

Calculate the percentage of any other impurity in the portion of Fluoxetine Hydrochloride taken:

Result = {r_iA /[r_TA + (D × r_UB )]} × 100

r_iA = peak response of any other impurity from Sample solution A

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

D = dilution factor between Sample solution A and Sample solution B, 5

r_UB = peak response of uoxetine from Sample solution B

Acceptance criteria: See Table 1. The reporting threshold is 0.05%. (USP 1-Dec-2019)

Table 1

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

^b This impurity may not be present.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Fluoxetine Hydrochloride RS

USP Fluoxetine Related Compound A RS

N-Methyl-3-phenyl-3-[3-(trifluoromethyl)phenoxy]propan-1-amine hydrochloride;

Also known as N-Methyl-3-phenyl-3-[(α,α,α-(trifluoro-m-tolyl)oxy]propylamine hydrochloride.

C₁₇H₁₈F₃NO · HCl 345.79

USP Fluoxetine Related Compound B RS

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

Also known as N-Methyl-3-phenylpropylamine.

C₁₀H₁₅N 149.24