Fluphenazine Hydrochloride 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

Fluphenazine Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fluphenazine hydrochloride (C₂₂H₂₆F₃N₃OS ·  2HCl).

[Note—Throughout the following procedures, protect samples, the Reference Standard, and solutions containing them by conducting the procedures without delay, under subdued light, or using low-actinic glassware.]

2 IDENTIFICATION

A. Thin-Layer Chromatography

Diluent: Methanol and water (80:20)

Standard solution: 20 mg/mL of USP Fluphenazine Hydrochloride RS in Diluent prepared as follows. Transfer 10 mg of USP Fluphenazine Hydrochloride RS to a separator. Add 5 mL of water and 20 mL of dilute hydrochloric acid (1 in 120) to the separator, shake for 10 min, and add 20 mL of chloroform-saturated sodium carbonate solution (1 in 10). Extract the resulting mixture with ve 20-mL portions of chloroform, shaking gently to avoid emulsion formation, and pass the extract through a chloroform-washed cotton filter into a 150-mL beaker. Evaporate the extract on a steam bath to dryness, and dissolve the residue in 0.5 mL of Diluent.

Sample solution: Nominally 20 mg/mL of fluphenazine hydrochloride from Tablets in Diluent prepared as follows. Transfer a portion of finely powdered Tablets, equivalent to 10 mg of fluphenazine hydrochloride, to a separator. Add 5 mL of water and 20 mL of dilute hydrochloric acid (1 in 120) to the separator, shake for 10 min, and add 20 mL of chloroform-saturated sodium carbonate solution (1 in 10). Extract the resulting mixture with ve 20-mL portions of chloroform, shaking gently to avoid emulsion formation, and pass the extract through a chloroform-washed cotton filter into a 150-mL beaker. Evaporate the extract on a steam bath to dryness, and dissolve the residue in 0.5 mL of Diluent.

2.1 Chromatographic system

(See Chromatography 〈621〉, General Procedures, Thin-Layer Chromatography.)

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Acetone, cyclohexane, and diethylamine (40:15:1)

Spray reagent: Sulfuric acid in methanol (2 in 5)

2.2 Analysis

Samples: Standard solution and Sample solution

Allow the spots to dry, and develop the chromatogram in the Developing solvent system until the solvent front has moved three-fourths of the length of the plate. Locate the spots on the plate by lightly spraying it with Spray reagent.

Acceptance criteria: The R value and color of the principal spot of the Sample solution correspond to those of the Standard solution.

3 ASSAY

Procedure

Buffer: 0.05 M monobasic potassium phosphate adjusted with phosphoric acid to a pH of 2.5

Diluent: Acetonitrile, methanol, and Buffer (30:30:40)

Mobile phase: 0.2% triethylamine in Diluent

Standard solution: 0.06 mg/mL of USP Fluphenazine Hydrochloride RS in Diluent

Sample stock solution: Transfer 6 Tablets to a suitable volumetric ask, add Diluent, shake for 1 h, and sonicate for 10 min or until a ne suspension is obtained.

Sample solution: Nominally 0.06 mg/mL of fluphenazine hydrochloride from Sample stock solution in Diluent. Filter, and use the ltrate after discarding the first 5 mL of the filtrate.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 12.5-cm; packing L7

Flow rate: 1 mL/min

Injection volume: 25 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 2000 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluphenazine hydrochloride (C₂₂H₂₆F₃N₃OS · 2HCl) in the portion of Tablets 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 Fluphenazine Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1 (RB 21-Jul-2020)

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 45 min

Buffer: 0.05 M monobasic potassium phosphate adjusted with phosphoric acid to a pH of 2.5

Diluent: Acetonitrile, methanol, and Buffer (30:30:40)

Mobile phase: 0.3% triethylamine in Diluent

Sample solution: Dilute a portion of the solution under test with an equal volume of Mobile phase.

Standard solution: USP Fluphenazine Hydrochloride RS at a concentration and composition similar to that of the Sample solution

Chromatographic system and System suitability: Proceed as directed in the Assay, except use a ow rate of 2 mL/min and an injection volume of 100 µL.

Analysis

Samples: Sample solution and Standard solution

Determine the amount of fluphenazine hydrochloride (C₂₂H₂₆F₃N₃OS · 2HCl) dissolved.

Tolerances: NLT 75% (Q) of the labeled amount of fluphenazine hydrochloride (C₂₂H₂₆F₃N₃OS· 2HCl) is dissolved.

4.2 Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 1: 100 rpm

Time: 30 min

Diluted phosphoric acid solution: Transfer 10 mL of phosphoric acid to a 100-mL volumetric ask containing about 50 mL of water. Cool and dilute with water to volume.

Buffer: 6.8 g/L of monobasic potassium phosphate in water, adjusted with Diluted phosphoric acid solution to a pH of 2.5 Solution A: Acetonitrile, methanol, and Buffer (30:30:40)

Mobile phase: To each liter of Solution A, add 3.0 mL of triethylamine.

Diluent: Medium and Mobile phase (50:50)

Standard stock solution: 0.1 mg/mL of USP Fluphenazine Hydrochloride RS in Diluent. Sonicate to dissolve if needed. Standard solution: (L/1000) mg/mL of USP Fluphenazine Hydrochloride RS from the Standard stock solution in Diluent, where L is the label claim in mg/Tablet

Sample stock solution: Pass a portion of the solution under test through an appropriate filter, and discard the first 2 mL of filtrate. Sample solution: Transfer an equal volume of the Sample stock solution and the Mobile phase to a suitable container, and mix well.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 5-cm; 3.5-µm packing L7

Column temperature: 40°

Flow rate: 2 mL/min

Injection volume: 100 µL

Run time: NLT 2 times the retention time of fluphenazine

4.2.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluphenazine hydrochloride (C₂₂H₂₆F₃N₃OS · 2HCl) dissolved:

Result = (r_U /r_S) × C_S × D × V × (1/L) × 100

r_U = peak response of fluphenazine from the Sample solution

r_S = peak response of fluphenazine from the Standard solution

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

D = dilution factor for the Sample solution, 2

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fluphenazine hydrochloride (C H F N OS · 2HCl) is dissolved. _{(RB 21-Jul-2020)}

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

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

Add the following:

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. (RB 21-Jul-2020)

USP Reference Standards 〈11〉

USP Fluphenazine Hydrochloride RS