Monographs: Pharmaceutical substances: Ethosuximide (Ethosuximidum)
Molecular formula. C7H11NO2
Relative molecular mass. 141.2
Chemical name. 2-Ethyl-2-methylsuccinimide; 3-ethyl-3-methyl-2,5-pyrrolidinedione; CAS Reg. No. 77-67-8.
Description. A white or almost white powder or waxy solid; odourless or with a faint characteristic odour.
Solubility. Freely soluble in water; very soluble in ethanol (~750 g/l) TS and ether R.
Storage. Ethosuximide should be kept in a tightly closed container, protected from light.
Additional information. Even in the absence of light, Ethosuximide is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures.
Definition. Ethosuximide contains not less than 99.0% and not more than 100.5% of C7H11NO2, calculated with reference to the anhydrous substance.
• Either test A alone or tests B and C may be applied.
Cyanides. Dissolve 1 g in 10 mL of ethanol (~750 g/l) TS, add 3 drops of ferrous sulfate (15 g/l) TS, 1 mL of sodium hydroxide (~80 g/l) TS and a few drops of ferric chloride (25 g/l) TS. Warm gently, and acidify with sulfuric acid (~100 g/l) TS; no blue precipitate or blue colour is produced within 15 minutes.
Sulfated ash. Not more than 5.0 mg/g.
Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using about 1 g of the substance; the water content is not more than 5.0 mg/g.
Acidity. Dissolve 5.0 g in 50 mL of water by warming on a water-bath for 5 minutes. Cool and titrate with sodium hydroxide (0.1 mol/l) VS, using bromocresol green/ethanol TS as indicator; not more than 0.7 mL is required to obtain the midpoint of the indicator (green).
Related substances. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R2 as the coating substance and a mixture of 9 volumes of chloroform R and 1 volume of acetone R as the mobile phase. Apply separately to the plate 10 μl of each of 2 solutions in ethanol (~750 g/l) TS containing (A) 50 mg of the test substance per mL and (B) 0.050 mg of the test substance per mL. After removing the plate from the chromatographic chamber allow it to dry in air, and examine the chromatogram in ultraviolet light (254 nm). Any spot obtained with solution A, other than the principal spot, is not more intense than that obtained with solution B.
Assay. Dissolve about 0.28 g, accurately weighed, in 30 mL of dimethylformamide R, add 3 drops of azo violet TS and titrate with tetrabutylammonium hydroxide (0.1 mol/l) VS to a blue end-point, as described under 2.6 Non-aqueous titration. Method B. Each mL of tetrabutylammonium hydroxide (0.1 mol/l) VS is equivalent to 14.12 mg of C7H11NO2.