ketoconazole-compounded-oral-suspension

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

Ketoconazole Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of ketoconazole (C₂₆H₂₈Cl₂N₄O₄).

Prepare Ketoconazole Compounded Oral Suspension 20 mg/mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

Place the required number of tablets in a glass mortar, and comminute to a fine powder such that they pass through a 40-mesh or 45-mesh sieve, or add Ketoconazole powder to the mortar. Dissolve the Cetylpyridinium Chloride in Purified Water, and dilute quantitatively, and stepwise if necessary, with Purified Water to obtain 10 mL of a solution containing 10 mg of Cetylpyridinium Chloride. Transfer this solution, individed portions, to the mortar containing the powder, and mix to form a smooth paste. Place 20 mL of Purified Water in a beaker. Using moderate heat, stir to form a vortex, and slowly sprinkle the Xanthan Gum into the vortex to obtain a uniform dispersion. Add the dispersion to the wetted powder paste, and mix until smooth. Add a sucient quantity of the Suspension Structured Vehicle or Sugar-Free Suspension Structured Vehicle to bring to final volume. Mix well.

2 ASSAY

Procedure

Mobile phase: Acetonitrile and 0.01 M tetrabutylammonium hydrogen sulfate (25:75). Pass through a filter of 5-μm or finer pore size, and degas.

Diluent: Methanol and water (50:50)

System suitability solution: Dissolve 4 mg of USP Ketoconazole RS in 1.0 mL of a solution of potassium sorbate in water (1 in 5000). Dilute with Diluent to 10.0 mL.

Standard solution: 0.4 mg/mL of USP Ketoconazole RS in Diluent

Sample solution: [Note—If the Oral Suspension has settled, invert the container 10–15 times, and sonicate for 5 min, or stir on a magnetic stirrer until the Oral Suspension appears homogeneous. Examine the mixture for the presence of bubbles and unsuspended solids before sampling.] Transfer 5.0 mL of homogeneous Oral Suspension to a 250-mL volumetric flask, add 100 mL of water, and stir for 15 min to dissolve the xanthan gum. Add 135 mL of methanol, and stir for an additional 15 min. Cool, and dilute with methanol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 223 nm

Columns

Guard: 5-μm packing L1

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

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 5 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for ketoconazole and sorbate are 1.0 and 1.7, respectively.]

Suitability requirements

Resolution: NLT 2.0 between sorbate and ketoconazole, System suitability solution

Relative standard deviation: NMT 2.0% for replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ketoconazole (C₂₆H₂₈Cl₂N₄O₄ ) in the portion of Oral Suspension taken:

Result = (r_U/r_S)x(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 Ketoconazole RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

3 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in tight, light-resistant containers. Store at controlled room temperature.

Beyond-Use Date: NMT 14 days after the date on which it was compounded when stored at controlled room temperature

Labeling: Label it to state that it is to be well shaken before use, and that it is to be protected from light. Label it to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Ketoconazole RS