Ethambutol Hydrochloride 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

Ethambutol Hydrochloride Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of ethambutol hydrochloride (C₁₀H₂₄N₂O₂ · 2HCl).

Prepare Ethambutol Hydrochloride Compounded Oral Suspension 100 mg/mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

^a Ethambutol Hydrochloride 100-mg tablet(s), Lupin Pharmaceuticals, Baltimore, MD.

^b Perrigo Laboratories, Allegan, MI.

Place the required number of tablets in a suitable container and comminute to a fine powder. Wet the powder with a small amount of Vehicle and triturate to make a smooth paste. Add the Vehicle to make the contents pourable. Transfer the contents stepwise and quantitatively to a calibrated container using the Vehicle. Add sufficient Vehicle to bring to final volume. Shake to mix well.

2 ASSAY

Procedure

Solution A: 0.1% triethylamine in water, adjusted with phosphoric acid to a pH of 7.0. Pass through a nylon filter of 0.45-μm pore size and degas.

Mobile phase: Acetonitrile and Solution A (50:50)

Diluent: 1.4 g/L of sodium phosphate in water adjusted with phosphoric acid to a pH of 6.8

Standard stock solution: 10 mg/mL of USP Ethambutol Hydrochloride RS in Diluent. Sonicate to mix well. Store at 2°–8°.

Standard solution: Transfer 0.25 mL of the Standard stock solution to a 5-mL volumetric flask, dilute with Diluent to volume, and mix well.

Transfer an aliquot to a centrifuge tube, and centrifuge for 5 min at 14,000 rpm at 2°–8°. Transfer the supernatant to an amber vial and store at 2°–8°.

Sample solution: Transfer 2 mL of Oral Suspension to a 20-mL volumetric flask, dilute with Diluent to volume, and sonicate to mix well.

Transfer 0.25 mL of the resultant solution to a 5-mL volumetric flask, dilute with Diluent to volume, and mix well. Transfer an aliquot to a centrifuge tube, and centrifuge for 5 min at 14,000 rpm at 2°–8°. Transfer the supernatant to an amber vial and store at 2°–8°.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV-Vis 200 nm

Column: 4.6-mm × 25-cm; 5-μm packing L10

Temperatures

Autosampler: 5°

Column: 30°

Flow rate: 1.3 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

[Note—The retention time for ethambutol hydrochloride is about 3.7 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ethambutol hydrochloride (C₁₀H₂₄N₂O₂ · 2HCl) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of ethambutol hydrochloride from the Sample solution

r_S = peak response of ethambutol hydrochloride from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 3.5–5.6

4 ADDITIONAL REQUIREMENTS

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

Beyond-Use Date: NMT 90 days after the date on which it was compounded when stored in a refrigerator or at controlled room temperature

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

USP Reference Standards 〈11〉

USP Ethambutol Hydrochloride RS