Hydroxyurea Capsules

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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click https://www.uspnf.com/rb-hydroxyurea-caps-20240426.

1 DEFINITION

Hydroxyurea Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of hydroxyurea (CH₄N₂O₂).

2 IDENTIFICATION

A.

Standard: Transfer 30 mg of USP Hydroxyurea RS to a suitable centrifuge tube, and add 10 mL of anhydrous methanol. Centrifuge for 3 min. Transfer 1.0 mL of the clear supernatant to a mortar containing 500 mg of potassium bromide, triturate to a homogeneous blend, dry in a vacuum desiccator at 60° for 3 h, and prepare a suitable disk.

Sample: Transfer a portion of Capsule contents, equivalent to 30 mg of hydroxyurea, to a suitable centrifuge tube, and add 10 mL of anhydrous methanol. Centrifuge for 3 min. Transfer 1.0 mL of the clear supernatant to a mortar containing 500 mg of potassium bromide, triturate to a homogeneous blend, dry in a vacuum desiccator at 60° for 3 h, and prepare a suitable disk.

Acceptance criteria: The IR absorption spectrum of the Sample exhibits maxima only at the same wavenumbers as that of the Standard.

3 ASSAY

3.1 PROCEDURE

Solution A: Dissolve 1.7 g of tetrabutylammonium hydrogen sulfate and 1.74 g of dibasic potassium phosphate in 1000 mL of water. Adjust with 1 N sodium hydroxide or phosphoric acid to a pH of 5.0.

Mobile phase: Methanol and Solution A (15:85)

System suitability solution: 0.4 mg/mL each of USP Hydroxyurea RS and hydroxylamine hydrochloride in Mobile phase

Standard solution: 0.4 mg/mL of USP Hydroxyurea RS in Mobile phase

Sample solution: Nominally 0.4 mg/mL of hydroxyurea in Mobile phase prepared as follows. Remove, as completely as possible, the contents of NLT 20 Capsules and grind to a fine powder. Transfer a portion of the powder, equivalent to 200 mg of hydroxyurea, to a 500-mL volumetric flask. Add 300 mL of Mobile phase, sonicate for 10 min, stir with the aid of a magnetic stirrer for 30 min, sonicate for an additional 10 min, and dilute with Mobile phase to volume. Filter a portion of the resulting solution, discarding the first 2 mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 0.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between hydroxylamine and hydroxyurea, System suitability solution

Column efficiency: NLT 5000 for hydroxyurea, System suitability solution

Tailing factor: NMT 1.5 for hydroxyurea, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyurea (CH₄N₂O₂) in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of hydroxyurea from the Sample solution

r_S = peak response of hydroxyurea from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

5 DISSOLUTION (711)

Test 1 (RB 27-Mar-2024)

Medium: Water; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Analysis: Calculate the percentage of the labeled amount of hydroxyurea (CH₄N₂O₂) dissolved by using the procedure set forth in the Assay, making any necessary modifications.

Tolerances: NLT 80% (Q) of the labeled amount of hydroxyurea (CH₄N₂O₂) is dissolved.

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 2: 50 rpm

Time: 30 min

Buffer: Dissolve 1.7 g of tetrabutylammonium hydrogen sulfate and 1.74 g of dibasic potassium phosphate in 1000 mL of water. Adjust with phosphoric acid to a pH of 5.0.

Mobile phase: Methanol and Buffer (15:85)

Standard solution: (L/500) mg/mL of USP Hydroxyurea RS in Medium, where L is the label claim in mg/Capsule

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 0.5 mL/min

Injection volume: 10 µL

Run time: NLT 4.5 times the retention time of hydroxyurea

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyurea (CH₄N₂O₂) dissolved:

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

r_U = peak response of hydroxyurea from the Sample solution

r_S = peak response of hydroxyurea from the Standard solution

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

V = volume of Medium, 500 mL

L = label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of hydroxyurea (CH₄N₂O₂) is dissolved. (RB 27-Mar-2024)

5.1 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, in a dry atmosphere.

Add the following:

LABELING: The labeling states the Dissolution test used only if Test 1 is not used. (RB 27-Mar-2024)

USP REFERENCE STANDARDS (11)

USP Hydroxyurea RS