Monographs: Pharmaceutical substances: Phenytoin (Phenytoinum)

Molecular formula. C15H12N2O2

Relative molecular mass. 252.3

Graphic formula.

Chemical name. 5,5-Diphenylhydantoin; 5,5-diphenyl-2,4-imidazolidinedione; CAS Reg. No. 57-41-0.

Description. A white, crystalline powder; odourless.

Solubility. Practically insoluble in water; sparingly soluble in ethanol (~750 g/l) TS; slightly soluble in ether R.

Category. Anticonvulsant.

Storage. Phenytoin should be kept in a tightly closed container, protected from light.

Requirements

Definition. Phenytoin contains not less than 98.0% and not more than 101.0% of C15H12N2O2, calculated with reference to the dried substance.

Identity tests

• Either test A or tests B, C, and D may be applied.

A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from phenytoin RS or with the reference spectrum of phenytoin.

B. Dissolve 20 mg in 2 mL of ammonia (~100 g/l) TS and add 5 mL of silver nitrate (40 g/l) TS; a white precipitate is produced.

C. Dissolve 5 mg in 1 mL of boiling ethanol (~750 g/l) TS, add 2 mL of water, 2 drops of pyridine R, and 2 drops of copper (II) sulfate (80 g/l) TS; allow to cool; a blue-violet, crystalline precipitate is produced.

D. Melting temperature, about 295°C.

Heavy metals. Use 1.0 g for the preparation of the test solution, as described under 2.2.3 Limit test for heavy metals, Procedure 3; determine the heavy metals content according to Method A; not more than 10 μg/g.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry to constant weight at 105°C; it loses not more than 10 mg/g.

Acidity or alkalinity. Shake 2 g for 1 minute with 40 mL of carbon-dioxide-free water R, and filter. To 10 mL of the filtrate add 2 drops of phenolphthalein/ethanol TS; no colour is produced. Add 0.15 mL of carbonate-free sodium hydroxide (0.01 mol/l) VS; a pink colour is produced. Add 0.3 mL of hydrochloric acid (0.01 mol/l) VS and 5 drops of methyl red/ethanol TS; a red or orange colour is produced.

Assay. Dissolve about 0.5 g, accurately weighed, in 50 mL of dimethylformamide R, add 2 drops of thymol blue/dimethylformamide TS and titrate with sodium methoxide (0.1 mol/l) VS to a blue end-point, as described under 2.6 Non-aqueous titration, Method B. Each mL of sodium methoxide (0.1 mol/l) VS is equivalent to 25.23 mg of C15H12N2O2.

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