Monographs: Pharmaceutical substances: Phenobarbital sodium (Phenobarbitalum natricum)

Molecular formula. C12H11N2NaO3

Relative molecular mass. 254.2

Graphic formula.

Chemical name. Sodium 5-ethyl-5-phenylbarbiturate; 5-ethyl-5-phenyl-2,4,6-(1H,3H,5H)-pyrimidinetrione monosodium salt; CAS Reg. No. 57-30-7.

Description. White, crystalline granules or a white, crystalline powder; odourless.

Solubility. Freely soluble in water; soluble in ethanol (~750 g/l) TS; practically insoluble in ether R

Category. Hypnotic; sedative; anticonvulsant.

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

Additional information. Phenobarbital sodium is hygroscopic. Even in the absence of light, Phenobarbital sodium is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures.

Requirements

Definition. Phenobarbital sodium contains not less than 98.0% and not more than 101.0% of C12H11N2NaO3, calculated with reference to the dried substance.

Identity tests

• Either tests A and D 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 reference spectrum of phenobarbital sodium.

B. Dissolve 0.2 g in 10 mL of water and add 2 mL of hydrochloric acid (~70 g/l) TS; a white, crystalline precipitate is produced. Wash the precipitate with water until free from chlorides, and dry at 105°C; melting temperature, about 175°C (phenobarbital). Keep the precipitate for test C.

C. Dissolve 20 mg of the precipitate obtained from test B in 5 mL of ethanol (~750 g/l) TS, add 1 drop of cobaltous chloride TS and 1 drop of ammonia (~100 g/l) TS; a violet colour is produced.

D. When tested for sodium as described under 2.1 General identification tests, yields the characteristic reactions. If reaction B is to be used, prepare a 20 mg/mL solution.

Clarity and colour of solution. A solution of 1.0 g in 10 mL of carbon-dioxide-free water R remains clear and colourless during 15 minutes.

Loss on drying. Dry to constant weight at 140°C; it loses not more than 70 mg/g.

pH value. pH of a 0.10 g/mL solution in carbon-dioxide-free water R, 9.0-10.8.

Neutral and basic impurities. Dissolve 1.0 g in a mixture of 5 mL of sodium hydroxide (~80 g/l) TS and 10 mL of water, and shake for 1 minute with 25 mL of ether R. Wash the ethereal layer 3 times, each time with 5 mL of water, evaporate the ether, and dry the residue at 105°C for 1 hour; the residue weighs not more than 3.0 mg.

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 80 volumes of chloroform R, 15 volumes of ethanol (~750 g/l) TS and 5 volumes of ammonia (~260 g/l) TS as the mobile phase. Apply separately to the plate 10 μl of each of 2 solutions in ethanol (~750 g/l) TS containing (A) 10 mg of the test substance per mL and (B) 0.20 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 0.5 g, accurately weighed, in 15 mL of water, add 5 mL of hydrochloric acid (2 mol/l) VS, and extract with 50 mL of ether R and then with successive quantities, each of 25 mL of ether R, until complete extraction has been effected. Wash the combined extracts twice with water, using 5 mL each time. Add the ether extract to the main ether extract, evaporate to low bulk, add 2 mL of dehydrated ethanol R, evaporate to dryness, and dry the residue to constant weight at 105°C. Each g of residue is equivalent to 1.095 g of C12H11N2NaO3.

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