Ethosuximide

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 contains NLT 98.0% and NMT 102.0% (USP 1-Aug-2022) of ethosuximide (C₇H₁₁NO₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A (USP 1-Aug-2022)

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

Change to read:

Procedure

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

Standard solution: 2.0 mg/mL of USP Ethosuximide RS in Mobile phase

Sample solution: 2.0 mg/mL of Ethosuximide in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 3.9-mm × 15-cm; 4-μm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of ethosuximide

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73% (USP 1-Aug-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ethosuximide (C₇H₁₁NO₂) in the portion of Ethosuximide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response of ethosuximide (USP 1-Aug-2022) from the Sample solution

r_S= peak response of ethosuximide (USP 1-Aug-2022) from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% (USP 1-Aug-2022) on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.5%

Change to read:

Organic Impurities

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

System suitability solution: 50 mg/mL of USP Ethosuximide RS and 0.25 mg/mL of USP Ethosuximide Related Compound A RS in Mobile phase

Sensitivity solution: 0.025 mg/mL of USP Ethosuximide RS in Mobile phase

Standard solution: 0.05 mg/mL each of USP Ethosuximide RS and USP Ethosuximide Related Compound A RS in Mobile phase

Sample solution: 50 mg/mL of Ethosuximide in Mobile phase. Sonicate as needed.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 3.9-mm × 15-cm; 4-μm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 5 times the retention time of ethosuximide

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note—See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between ethosuximide and ethosuximide related compound A, System suitability solution

Relative standard deviation: NMT 5.0% for ethosuximide and ethosuximide related compound A, Standard solution Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ethosuximide related compound A in the portion of Ethosuximide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of ethosuximide related compound A from the Sample solution

r_S = peak response of ethosuximide related compound A from the Standard solution

C_S = concentration of USP Ethosuximide Related Compound A RS in the Standard solution (mg/mL)

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

Calculate the percentage of each unspecified impurity in the portion of Ethosuximide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = peak response of ethosuximide from the Standard solution

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

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

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.5%

Change to read:

Limit of Cyanide

Sample solution: 100 mg/mL of Ethosuximide (USP 1-Aug-2022) in alcohol

Analysis: To 10 mL of Sample solution, add 3 drops of ferrous sulfate TS, 1 mL of 1 N sodium hydroxide VS, and a few drops of ferric chloride TS. Warm gently, and acidify with 2 N sulfuric acid TS.

Acceptance criteria: No blue precipitate or blue color is formed within 15 min.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Change to read:

USP Reference Standards 〈11〉

USP Ethosuximide RS

USP Ethosuximide Related Compound A RS

2-Ethyl-2-methylsuccinic acid

C₇H₁₂O₄ 160.17 (USP 1-Aug-2022)