Fludrocortisone Acetate 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

Fludrocortisone Acetate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fludrocortisone acetate (C₂₃H₃₁FO₆).

2 IDENTIFICATION

Delete the following:

A. Thin-Layer Chromatography

Standard solution: 100 µg/mL of USP Fludrocortisone Acetate RS in acetone

Sample solution: Nominally 0.1 mg/mL of fludrocortisone acetate from Tablets prepared as follows. Transfer a portion of powdered Tablets, equivalent to 1 mg of fludrocortisone acetate, to a glass stoppered centrifuge tube, add 10 mL of acetone, and shake by mechanical means for 3 min. Centrifuge the mixture. Use the clear solution.

2.1 Chromatographic system

(See Chromatography 〈621〉.)

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volumes Standard solution: 20 µL

Sample solution: 20 µL, in 5-µL increments

Developing solvent system: Chloroform, methanol, and water (85:14:1)

2.2 Analysis

Samples: Standard solution and Sample solution

Apply the Samples in a line parallel to and about 2.5 cm from the bottom of the plate. Develop the plate in a chamber using the Developing solvent system until the solvent front has moved about 15 cm. Remove the plate, air-dry, and examine under short-wavelength UV light. Acceptance criteria: The R_F value of the principal spot of the Sample solution corresponds to that of the Standard solution. 2S (USP41)

Add the following:

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.2S (USP41)

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.2S (USP41)

3 ASSAY

Change to read:

Procedure

Throughout the following procedures protect the solutions containing samples or Reference Standards from light.

Mobile phase: Acetonitrile, water, and phosphoric acid (40: 60: 0.1)

Standard stock solution: 0.2 mg/mL of USP Fludrocortisone Acetate RS in acetonitrile

Standard solution: 4 µg/mL of USP Fludrocortisone Acetate RS from Standard stock solution in Mobile phase Sample solution: Nominally 4 µg/mL of fludrocortisone acetate from Tablets prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric ask, and add 80% of the nal ask volume of Mobile phase. Stir for 20 min, and dilute with Mobile phase to volume. Pass the resulting solution through a suitable filter, discarding the first 5 mL of the filtrate.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 50 µL

Run time: NLT 1.4 times the retention time of fludrocortisone acetate

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.7 for fludrocortisone acetate

Relative standard deviation: NMT 1.0% for fludrocortisone acetate

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fludrocortisone acetate (C₂₃H₃₁FO₆) 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 Fludrocortisone Acetate RS in the Standard solution (µg/mL)

C_U = nominal concentration of fludrocortisone acetate in the Sample solution (µg/mL)2S (USP41)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Throughout the following procedures protect the solutions containing samples or Reference Standards from light.2S (USP41) Medium: 0.01 N hydrochloric acid TS;2S (USP41) 500 mL

Apparatus 2: 75 rpm Time: 30 min

Mobile phase: Acetonitrile and water (45:55)

Standard stock solution: 0.025 mg/mL of USP Fludrocortisone Acetate RS prepared as follows. Transfer an appropriate amount of USP Fludrocortisone Acetate RS to a suitable volumetric ask. Add 5% of the ask volume of acetonitrile, sonicate for 5 min to promote dissolution, and dilute with Medium to volume.

Standard solution: (L/500) mg/mL of USP Fludrocortisone Acetate RS from Standard stock solution in Medium, where L is the label claim in mg/Tablet2S (USP41)

Sample solution: Withdraw a portion of the solution under test with glass syringes, and pass through a membrane filter that has been checked for absorptive loss.

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm2S (USP41)

Column: 4.6-mm × 15-cm; 5-µm2S (USP41) packing L1

Flow rate: 2 mL/min

Injection volume: 100 µL

4.2 System suitability

Sample: Standard solution

Suitability requirements

2S (USP41)

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fludrocortisone acetate (C₂₃H₃₁FO₆) dissolved:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fludrocortisone Acetate RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)2S (USP41)

Tolerances: NLT 80% (Q) of the labeled amount of fludrocortisone acetate (C₂₃H₃₁FO₆) is dissolved.

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements

2S (USP41)

5 IMPURITIES

Change to read:

Organic Impurities

Throughout the following procedures protect the solutions containing samples or Reference Standards from light. Mobile phase: Acetonitrile, water, and phosphoric acid (40: 60: 0.1)

Standard stock solution: 0.40 mg/mL of USP Fludrocortisone Acetate RS in acetonitrile

Standard solution: 0.4 µg/mL of USP Fludrocortisone Acetate RS from Standard stock solution in Mobile phase

Sensitivity solution: 0.04 µg/mL of USP Fludrocortisone Acetate RS from Standard solution in Mobile phase

Sample solution: Nominally 80 µg/mL of fludrocortisone acetate from Tablets prepared as follows. Transfer NLT 20 Tablets to a suitable volumetric ask, add 80% of the nal volume of Mobile phase, and stir for 20 min. Dilute with Mobile phase to volume. Centrifuge a portion of the solution and use the supernatant. [Note—The use of a centrifuge speed of 4000 rpm for 10 min may be suitable.]

5.1 Chromatographic system

Proceed as directed in the Assay, except for the Run time.

Run time: NLT 2.7 times the retention time of fludrocortisone acetate

5.2 System suitability

Samples: Standard solution and Sensitivity solution

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

Suitability requirements

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Signal-to-noise ratio: NLT 10.0, Sensitivity solution

5.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

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

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of fludrocortisone acetate from the Standard solution

C_S = concentration of USP Fludrocortisone Acetate RS in the Standard solution (µg/mL)

C_U = nominal concentration of fludrocortisone acetate in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

^a 9-Fluoro-11β,17,21-trihydroxypregn-4-ene-3,20-dione. (ERR 1-Mar-2019)

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.2S (USP41)

Change to read:USP Reference Standards 〈11〉

USP Fludrocortisone Acetate RS

_{2S (USP41)}