Ethambutol Hydrochloride 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

Ethambutol Hydrochloride Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of ethambutol hydrochloride (C₁₀H₂₄N₂O₂ · 2HCl).

2 IDENTIFICATION

Sample: Triturate a quantity equivalent to 100 mg of ethambutol from powdered Tablets, with 3 mL of methanol in a glass mortar. Add 5 mL of methanol to obtain a suspension, then pass through a funnel lined with a suitable filter paper (Whatman No. 42 or equivalent) previously moistened with methanol, and collect the filtrate in a beaker containing 100 mL of acetone. Stir the mixture, and allow crystallization to proceed for 15 min. Decant the liquid, and gently dry the crystals with the aid of a current of air until the odor of methanol is no longer detectable: a portion of the crystals so obtained responds to the following tests.

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. Identification Tests—General, Chloride〈191〉

Sample solution: 100 mg/mL in water

Acceptance criteria: Meet the requirement

3 ASSAY

Procedure

Buffer: Mix 1.0 mL of triethylamine with 1 L of water, and adjust with phosphoric acid to pH 7.0.

Mobile phase: Acetonitrile and Buffer (1:1)

Standard solution: 0.30 mg/mL of USP Ethambutol Hydrochloride RS

Sample solution: Equivalent to 0.30 mg/mL of ethambutol hydrochloride from powdered Tablets (NLT 20). Filter the solution, discarding the first 10-mL portion.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 4.6-mm × 15-cm base-deactivated; 5-μm packing L10

Flow rate: 1 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ethambutol hydrochloride (C₁₀H₂₄N₂O₂ · 2HCl) present 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 Ethambutol Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Time: 45 min

Buffer: 38.0 g/L of monobasic sodium phosphate and 2.0 g/L of anhydrous dibasic sodium phosphate

Bromocresol green solution: Dissolve 200 mg of bromocresol green in 30 mL of water and 6.5 mL of 0.1 N sodium hydroxide. Dilute with Buffer to 500 mL, and add 0.1 N hydrochloric acid to adjust to a pH of 4.6 ± 0.1.

Standard solution: 0.1 mg/mL of USP Ethambutol Hydrochloride RS

Sample solution: Pass a portion of solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: Vis

Analytical wavelength: 415 nm

Analysis

Samples: Standard solution, Sample solution, and water (blank)

Into 3 separate, glass-stoppered, 50-mL centrifuge tubes, pipet 1 mL of water to provide the blank, 1 mL of Standard solution, and 1 mL of Sample solution. Add 5.0 mL of Bromocresol green solution to each tube, add 10.0 mL of chloroform to each, insert the stoppers, and shake the mixtures vigorously. Allow the mixtures to separate, discard the upper aqueous layers, and filter the 3 chloroform layers through separate pledgets of cotton.

Determine the the percentage of the labeled amount of ethambutol hydrochloride (C H N O · 2HCl) dissolved, using the blank to set the instrument.

Tolerances: NLT 75% (Q) of the labeled amount of C₁₀H₂₄N₂O₂ · 2HCl is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Limit of Aminobutanol

Buffer: 1.24 g of boric acid to a 100-mL volumetric flask. Dissolve in 90 mL of water, adjust with 5 N sodium hydroxide to a pH of 9.0, and dilute with water to volume.

Fluorescamine solution: 0.1 mg/mL offluorescamine in acetone

Standard solution: 5.0 μg/mL of USP Aminobutanol RS in water

Sample solution: Place a number of Tablets, equivalent to 400 mg of ethambutol hydrochloride, in a beaker, cover with acetone, and allow to stand for 15 min. Decant the acetone, dry the Tablets, and remove the coating. Grind the Tablet cores in a mortar to a fine powder, moisten with methanol, and triturate to a fine paste. Transfer the mixture with the aid of methanol to a 100-mL volumetric flask, dilute with methanol to volume, and mix. Pass the mixture through a dry, folded filter paper. Pipet 25 mL of the filtrate into a 200-mL volumetric flask, and dilute with water to volume. Allow to stand for 15 min, and pass through a dry, folded filter paper, discarding the first cloudy portions of the filtrate.

The clear filtrate is the Sample solution.

Instrumental conditions

(See Fluorescence Spectroscopy 〈853〉.)

Mode: Fluorometry

Analytical wavelength: Excitation wavelength at about 385 nm; emission wavelength at 485 nm

Cell: 1 cm

Analysis

Samples: Standard solution and Sample solution

Pipet a 10-mL portion of the Sample solution into a glass-stoppered, 100-mL conical flask, and add 10 mL of water and 20 mL of Buffer.

To another 100-mL flask, add 10.0 mL of the Sample solution, 10.0 mL of the Standard solution, and 20 mL of Buffer. Place the flasks on a magnetic stirrer, and while the contents are being stirred rapidly, add 10 mL of Fluorescamine solution rapidly. Insert the stoppers in the flasks, invert, and shake briefly. After 1 min, accurately timed, determine the relative fluorescence intensities of both solutions.

Acceptance criteria: The fluorescence intensity of the solution from the Sample solution is NMT the difference between the intensities of the two solutions; NMT 1.0%.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Aminobutanol RS

USP Ethambutol Hydrochloride RS