Sodium-Valproate-5571[英国药典BP2009]

Sodium Valproate General Notices

(Ph Eur monograph 0678)

IDENTIFICATION

A. Infrared absorption spectrophotometry (2.2.24).

Comparison sodium valproate CRS.

If the spectra obtained in the solid state show differences, record new spectra using discs prepared by placing 50 µl of a 100 g/l solution in methanol R on a disc of potassium bromide R and evaporating the solvent in vacuo. Examine immediately.

B. Examine the chromatograms obtained in the test for related substances.

Results The principal peak in the chromatogram obtained with test solution (b) is similar in retention time to the principal peak in the chromatogram obtained with reference solution (b).

C. 2 ml of solution S (see Tests) gives reaction (a) of sodium (2.3.1) .

TESTS

Solution S

Dissolve 1.25 g in 20 ml of distilled water R in a separating funnel, add 5 ml of dilute nitric acid R and shake. Allow the mixture to stand for 12 h. Use the lower layer.

Appearance of solution

The solution is not more opalescent than reference suspension II (2.2.1) and not more intensely coloured than reference solution Y6(2.2.2, Method II).

Dissolve 2.0 g in water R and dilute to 10 ml with the same solvent.

Acidity or alkalinity

Dissolve 1.0 g in 10 ml of water R. Add 0.1 ml of phenolphthalein solution R . Not more than 0.75 ml of 0.1 M hydrochloric acid or 0.1 M sodium hydroxide is required to change the colour of the indicator.

Related substances

Gas chromatography (2.2.28).

Internal standard solution Dissolve 10 mg of butyric acid R in heptane R and dilute to 200 ml with the same solvent.

Test solution (a) Dissolve 0.500 g of the substance to be examined in 10 ml of water R . Add 5 ml of dilute sulphuric acid R and shake with 3 quantities, each of 20 ml, of heptane R. Add 10.0 ml of the internal standard solution to the combined upper layers, shake with anhydrous sodium sulphate R , filter and evaporate the filtrate, at a temperature not exceeding 30 °C, using a rotary evaporator. Take up the residue with heptane R and dilute to 10.0 ml with the same solvent. Dilute 1.0 ml of this solution to 10.0 ml with heptane R .

Test solution (b) Dissolve 40 mg of the substance to be examined in 100 ml of water R . To 10 ml of this solution add 0.5 ml of dilute sulphuric acid R and shake with 3 quantities, each of 5 ml, of heptane R . Shake with anhydrous sodium sulphate R, filter and evaporate the filtrate, at a temperature not exceeding 30 °C, to a volume of about 10 ml, using a rotary

evaporator.

Reference solution (a) Dissolve 20 mg of 2-(1-methylethyl)pentanoic acid CRS (impurity C) in 5.0 ml of test solution (b) and dilute to 10 ml with heptane R . Dilute 1 ml of this solution to 10 ml with heptane R.

Reference solution (b) Prepare as prescribed for test solution (b), using sodium valproate CRS instead of the substance to be examined.

Column:

— material: wide-bore fused silica;

— size: l = 30 m, Ø = 0.53 mm;

— stationary phase: macrogol 20 000 2-nitroterephthalate R (film thickness 0.5 µm). Carrier gas helium for chromatography R.

Flow rate 8 ml/min.

Temperature:

Detection Flame ionisation.

Injection 1 µl.

System suitability Reference solution (a):

— resolution: minimum 3.0 between the peaks due to impurity C and valproic acid.

Limits Test solution (a):

— any impurity: for each impurity, not more than the area of the peak due to the internal standard (0.1 per cent);

— total: not more than 3 times the area of the peak due to the internal standard (0.3 per cent);

— disregard limit: 0.1 times the area of the peak due to the internal standard (0.01 per cent).

Chlorides (2.4.4)

Maximum 200 ppm.

To 5 ml of solution S add 10 ml of water R.

Sulphates (2.4.13)

Maximum 200 ppm, determined on Solution S.