Ethosuximide Oral Solution

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

Ethosuximide Oral Solution contains NLT 90.0% and NMT 105.0% of the labeled amount of ethosuximide (C₇H₁₁NO₂).

2 IDENTIFICATION

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

Standard solution: 30.0 mg/mL of USP Ethosuximide RS in chloroform

Sample solution: Nominally 30 mg/mL of ethosuximide in chloroform prepared as follows. Transfer the equivalent of about 150 mg of ethosuximide from Oral Solution to a 125-mL separatory funnel, add 50 mL of ether, and shake well. Allow the layers to separate, and retain the ether layer. Wash the ether layer with three 10-mL portions of water. Transfer the ether layer to a suitable beaker, add 5 g of anhydrous sodium sulfate, and swirl. Filter the mixture into a 50-mL volumetric flask through a small pledget of cotton that has been previously washed with ether. Evaporate to dryness. Dissolve the residue in 5 mL of chloroform.

Wavelength range: 3000–1650 cm−1

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: Meets the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

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Procedure

Mobile phase: Acetonitrile and water (12.5:87.5). To each liter, add 1.0 mL of glacial acetic acid.

System suitability solution: 0.062 mg/mL of USP Ethosuximide RS and 0.064 mg/mL of 2-ethyl-2-methylsuccinic acid in Mobile phase

Standard solution: 0.062 mg/mL of USP Ethosuximide RS in Mobile phase

Sample solution: Nominally 0.062 mg/mL of ethosuximide from Oral Solution in Mobile phase prepared as follows. Transfer a volume of Oral Solution, equivalent to 250 mg of ethosuximide, to a 100-mL volumetric flask. Dilute with Mobile phase to volume. Transfer 5.0 mL of this solution to a 200-mL volumetric flask and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 3.9-mm × 15-cm; 4-μm (USP 1-May-2019) packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of ethosuximide (USP 1-May-2019)

System suitability

Sample: System suitability solution

[Note—The relative retention times for ethosuximide and 2-ethyl-2-methylsuccinic acid are 1.0 and 1.3, respectively.] (USP 1-May-2019)

Suitability requirements

Resolution: NLT 3.5 between ethosuximide and 2-ethyl-2-methylsuccinic acid

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0% (USP 1-May-2019) for ethosuximide and NMT 5.0% for 2-ethyl-2-methylsuccinic acid

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ethosuximide (C₇H₁₁NO₂) in the portion of Oral Solution 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 Ethosuximide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–105.0%

4 IMPURITIES

Limit of 2-Ethyl-2-Methylsuccinic Acid

Mobile phase, System suitability solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard solution: 0.05 mg/mL of 2-ethyl-2-methylsuccinic acid in Mobile phase

Sample solution: Nominally 2.5 mg/mL of ethosuximide from Oral Solution in Mobile phase prepared as follows. Using a “to contain” pipet, transfer a volume of Oral Solution, equivalent to 250 mg of ethosuximide, to a 100-mL volumetric flask. Rinse the pipet several times with Mobile phase, and dilute with Mobile phase to volume.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 2-ethyl-2-methylsuccinic acid in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of 2-ethyl-2-methylsuccinic acid from the Sample solution

r_S = peak response of 2-ethyl-2-methylsuccinic acid from the Standard solution

C_S = concentration of 2-ethyl-2-methylsuccinic acid in the Standard solution (mg/mL)

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

Acceptance criteria: NMT 2.0%

5 SPECIFIC TESTS

pH 〈791〉: 4.5–5.8

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in tight containers. Store at controlled room temperature. Protect from freezing and light. (USP 1-May-2019)

USP Reference Standards 〈11〉

USP Ethosuximide RS