Ethosuximide
(eth'' oh sux' i mide).
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141.172,5-Pyrrolidinedione, 3-ethyl-3-methyl-, (±)-.
(±)-2-Ethyl-2-methylsuccinimide.
[77-67-8].» Ethosuximide contains not less than 98.0 percent and not more than 101.0 percent of C7H11NO2, calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
USP Reference standards 
11
—
11—
USP Ethosuximide RS 
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Identification—
Melting range 741:
between 47
and 52.
741:
between 47 and 52.
Water, Method I921:
not more than 0.5%.
921:
not more than 0.5%.
Residue on ignition 281:
not more than 0.5%.
281:
not more than 0.5%.
Limit of cyanide—
Dissolve 1 g in 10 mL of alcohol, and add 3 drops of ferrous sulfate TS, 1 mL of 1 N sodium hydroxide, and a few drops of ferric chloride TS. Warm gently, and acidify with 2 N sulfuric acid: no blue precipitate or blue color is formed within 15 minutes.
Limit of 2-ethyl-2-methylsuccinic acid and other impurities—
pH 3.0 Phosphate buffer, Mobile phase, System suitability solution, and Chromatographic system—
Proceed as directed in the Assay.
Standard solution—
Dissolve accurately weighed quantities of USP Ethosuximide RS and 2-ethyl-2-methylsuccinic acid in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.1 mg of each per mL.
Test solution—
Transfer about 1 g of Ethosuximide, accurately weighed, into a 10-mL volumetric flask, dissolve in Mobile phase, sonicating if necessary, dilute with Mobile phase to volume, and mix.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for all the peaks with an area greater than 0.1% of the total area, except the ethosuximide peak. Calculate the percentage of 2-ethyl-2-methylsuccinic acid in the portion of Ethosuximide taken by the formula:
(C / W)(ri / rS)
in which C is the concentration, in mg per mL, of 2-ethyl-2-methylsuccinic acid in the Standard solution; W is the weight, in g, of Ethosuximide taken to prepare the Test solution; and ri and rS are the peak responses of 2-ethyl-2-methylsuccinic acid obtained from the Test solution and the Standard solution, respectively: not more than 0.1% is found. Calculate the percentage of any other impurity in the portion of Ethosuximide taken by the formula:
(C / W)(ri / rS)
in which C is the concentration, in mg per mL, of USP Ethosuximide RS in the Standard solution; W is the weight, in g, of Ethosuximide taken to prepare the Test solution; ri is the peak response for each impurity obtained from the Test solution other than 2-ethyl-2-methylsuccinic acid; and rS is the peak response for ethosuximide obtained from the Standard solution: not more than 0.1% of any other impurity is found; and not more than 0.5% of total impurities is found.
Assay—
pH 3.0 Phosphate buffer—
Add 4.1 mL of phosphoric acid to 1000 mL of water, and adjust with sodium hydroxide TS to a pH of 3.0.
Mobile phase—
Prepare a filtered and degassed mixture of pH 3.0 Phosphate buffer and acetonitrile (90:10). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
System suitability solution—
Dissolve suitable quantities of 2-ethyl-2-methylsuccinic acid and USP Ethosuximide RS in an appropriate volume of Mobile phase to obtain a solution containing about 2 mg per mL and 10 mg per mL, respectively.
Standard preparation—
Dissolve an accurately weighed quantity of USP Ethosuximide RS in Mobile phase, and dilute with Mobile phase to obtain a solution having a known concentration of about 10.0 mg per mL.
Assay preparation—
Transfer about 100 mg of Ethosuximide to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm × 30.0-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between 2-ethyl-2-methylsuccinic acid and ethosuximide is not less than 6.6; the column efficiency determined from ethosuximide is not less than 2900 theoretical plates; the tailing factor for the ethosuximide peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 0.4%.
621)—
The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm × 30.0-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between 2-ethyl-2-methylsuccinic acid and ethosuximide is not less than 6.6; the column efficiency determined from ethosuximide is not less than 2900 theoretical plates; the tailing factor for the ethosuximide peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 0.4%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C7H11NO2 in the portion of Ethosuximide taken by the formula:
10C(rU / rS)
in which C is the concentration, in mg per mL, of USP Ethosuximide RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3131