Monographs: Pharmaceutical substances: Phenytoin (Phenytoinum)
Molecular formula. C15H12N2O2
Relative molecular mass. 252.3
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.
Storage. Phenytoin should be kept in a tightly closed container, protected from light.
Definition. Phenytoin contains not less than 98.0% and not more than 101.0% of C15H12N2O2, calculated with reference to the dried substance.
• Either test A or tests B, C, and D may be applied.
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.