Fluphenazine Decanoate Injection

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 Decanoate Injection is a sterile solution of Fluphenazine Decanoate in a suitable vegetable oil. It contains NLT 90.0% and NMT 115.0% of the labeled amount of fluphenazine decanoate (C₃₂H₄₄F₃N₃O₂S).

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

2 IDENTIFICATION

A.

Solution A: Palladium chloride solution (1 in 1000)

Sample: Nominally 50 mg of fluphenazine decanoate from Injection

Analysis

Part 1: Add 2 mL of methanol and 3 mL of Solution A to the Sample.

Part 2: Add an excess of Solution A to the resulting mixture from Part 1.

Acceptance criteria: The criteria for Part 1 and Part 2 must both be met.

Part 1: A rust-red color is produced.

Part 2: The color is intensified to a brownish red.

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

Change to read:

3.1 Procedure

Mobile phase: Acetonitrile, methanol, and 0.05 M ammonium acetate (2:2:1)

Diluent: Acetonitrile and methanol (50:50)

System suitability stock solution: USP Fluphenazine Decanoate Dihydrochloride RS and USP Fluphenazine Hydrochloride RS (5:4) in Diluent

System suitability solution: 0.1 mg/mL of anhydrous fluphenazine decanoate dihydrochloride and 0.08 mg/mL of fluphenazine hydrochloride from System suitability stock solution in Diluent

Standard stock solution A: 0.1 mg/mL of USP Fluphenazine Hydrochloride RS in isopropyl alcohol

Standard stock solution B: 0.5 mg/mL of USP Fluphenazine Decanoate Dihydrochloride RS and 0.02 mg/mL of fluphenazine hydrochloride from Standard stock solution A prepared as follows. Transfer 25 mg of USP Fluphenazine Decanoate Dihydrochloride RS to a 50-mL volumetric flask, and add 10 mL of Standard stock solution A. Add 20 mL of isopropyl alcohol. Sonication may be used to aid in dissolution. Dilute with isopropyl alcohol to volume.

Standard solution: 0.1 mg/mL of fluphenazine decanoate and 0.004 mg/mL of fluphenazine hydrochloride from Standard stock solution B in acetonitrile

Sample stock solution: Nominally 0.5 mg/mL of fluphenazine decanoate in isopropyl alcohol prepared as follows. Transfer a quantity of Injection, equivalent to 25 mg of fluphenazine decanoate, to a 50-mL volumetric fl ask. Add 20 mL of isopropyl alcohol, and shake vigorously for at least 1 min. Add 20 mL more of isopropyl alcohol, and repeat the vigorous shaking. Dilute with isopropyl alcohol to volume.

Sample solution: Nominally 0.1 mg/mL of fluphenazine decanoate from Sample stock solution in acetonitrile

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

3.3 Columns

Guard: 4.6-mm × 5-cm; 30- to 40-μm packing L1

Analytical: 4.6-mm × 25-cm; 10-μm packing L1

Flow rate: 2 mL/min

Injection volume: 20 μL

Run time: 2.5 times the retention time of fluphenazine decanoate

3.4 System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for fluphenazine and fluphenazine decanoate are about 0.6 and 1.0, respectively.]

3.5 Suitability requirements

Resolution: NLT 3.0 between fluphenazine and fluphenazine decanoate, System suitability solution

Relative standard deviation: NMT 2.0% for fluphenazine decanoate, Standard solution

3.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluphenazine decanoate (C H F N O S) in the portion of Injection taken:

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

r_U = peak response of fluphenazine decanoate from the Sample solution

r_S = peak response of fluphenazine decanoate from the Standard solution

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

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

M_r1 = molecular weight of fluphenazine decanoate, 591.78 (CN 1-May-2024)

M_r2 = molecular weight of fluphenazine decanoate dihydrochloride, 664.69 (CN 1-May-2024)

Acceptance criteria: 90.0%–115.0%

4 IMPURITIES

Change to read:

Limit of Fluphenazine and Late-Eluting Impurities

Analysis: Using the chromatograms from the Assay, calculate the percentage of fluphenazine in the portion of Injection taken:

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

r_U = peak height of fluphenazine from the Sample solution

r_U = peak height of fluphenazine from the Standard solution

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

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

M = molecular weight of fluphenazine, 437.53 (CN 1-May-2024)

M = molecular weight of fluphenazine hydrochloride, 510.44

Calculate the percentage of each impurity eluting after fluphenazine decanoate in the portion of Injection taken:

Result = (r_U/r_T) × 100

r_U = peak height of each impurity eluting after fluphenazine decanoate from the Sample solution

r_T = sum of the peak heights of fluphenazine decanoate and all the impurities eluting after fluphenazine decanoate from the Sample solution

Acceptance criteria

Fluphenazine: NMT 4%

Total impurities eluting after fluphenazine decanoate: NMT 2%

5 SPECIFIC TESTS

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Fluphenazine Hydrochloride RS

USP Fluphenazine Decanoate Dihydrochloride RS