Sodium Valproate Tablets

General Notices

Sodium Valproate Tablets from different manufacturers, whilst complying with the requirements of the monograph, may not be interchangeable.

Action and use

Antiepileptic.

Definition

Sodium Valproate Tablets contain Sodium Valproate.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of sodium valproate, C8H15NaO2

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 0.5 g of Sodium Valproate with 10 mL of water and centrifuge. Acidify 5 mL of the supernatant liquid with 2m sulfuric acid, shake with 25 mL of dichloromethane and wash the dichloromethane layer with 5 mL of water. Dry by shaking with anhydrous sodium sulfate, filter and evaporate the dichloromethane. The infrared absorption spectrum of a thin film of the residue, Appendix II A, is concordant with the reference spectrum of valproic acid (RS 431).
B. Shake a quantity of the powdered tablets containing 0.25 g of Sodium Valproate with 3 mL of water and centrifuge. To 2 mL of the supernatant liquid add 0.5 mL of a 10% w/v solution of cobalt(ii) nitrate. A purple precipitate is produced which is soluble in dichloromethane.

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of phosphate buffer pH 6.8, at a temperature of 37°, as the medium.
procedure

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) After 45 minutes withdraw a 20-mL sample of the medium and filter. Use the filtrate diluted, if necessary, to give a solution expected to contain 0.002% w/v of Sodium Valproate.
(2) 0.002% w/v of sodium valproate BPCRS in phosphate buffer pH 6.8.
chromatographic conditions
(a) Use a stainless steel column (30 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (µBondapak C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 50 µL of each solution.
mobile phase

45 volumes of a 0.32% w/v solution of potassium dihydrogen orthophosphate adjusted to pH 3.0 with orthophosphoric acid and 55 volumes of acetonitrile.

determination of content

Calculate the total content of sodium valproate, C8H15NaO2, in the medium from the chromatogram obtained and using the declared content of C8H15NaO2 in sodium valproate BPCRS.

Related substances

Carry out the method for gas chromatography, Appendix III B, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 0.50 g of Sodium Valproate with 10 mL of water, acidify with 2m sulfuric acid and shake with three 20-mL quantities of heptane. Wash the combined heptane extracts with 10 mL of water, shake with anhydrous sodium sulfate, filter, and dilute to 100 mL with heptane.
(2) Dilute 1 volume of solution (1) to 100 volumes with heptane and further dilute 1 volume of the resulting solution to 10 volumes with heptane.
(3) 0.5% w/v of valproate acid for system suitability EPCRS in heptane.
chromatographic conditions
(a) Use a fused silica capillary column (30 m × 0.53 mm) bonded with a 0.5-µm layer of macrogol 20,000 2-nitroterephthalate (DB-FFAP is suitable).
(b) Use helium as the carrier gas at 8 mL per minute.
(c) Use the temperature gradient conditions as described below.
(d) Use an injection temperature of 220°.
(e) Use a flame ionisation detector at 220°.
(f) Inject 1 µL of each solution.
system suitability

Inject solution (2) six times. The test is not valid unless the relative standard deviation of the area of the principal peak is at most 2.0%.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity K and valproic acid is at least 2.0.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of any secondary peaks is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.4%).

Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

Assay

Carry out the method for gas chromatography, Appendix III B, using the following prepared solutions.

(1) Weigh and powder 20 tablets. Shake a quantity of the powdered tablets containing 0.50 g of Sodium Valproate with 10 mL of water, acidify with 2m sulfuric acid and shake with three 20-mL quantities of heptane. Wash the combined heptane extracts with 10 mL of water, shake with anhydrous sodium sulfate, filter and dilute to 100 mL with heptane. Dilute 1 volume of this solution to 10 volumes with heptane.
(2) Shake 0.50 g of sodium valproate BPCRS with 10 mL of water, acidify with 2m sulfuric acid and shake with three 20-mL quantities of heptane. Wash the combined heptane extracts with 10 mL of water, shake with anhydrous sodium sulfate, filter and dilute to 100 mL with heptane. Dilute 1 volume of this solution to 10 volumes with heptane.
(3) 0.5% w/v of valproic acid for system suitability EPCRS in heptane.
chromatographic conditions

The chromatographic conditions described under the test for Related substances may be used.

system suitability

Inject solution (2) six times. The test is not valid unless the relative standard deviation of the area of the principal peak is at most 2.0%.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity K and valproic acid is at least 2.0.

determination of content

Calculate the content of C8H15NaO2 in the tablets using the declared content of C8H15NaO2 in sodium valproate BPCRS.

Impurities

The impurities limited by the requirements of this monograph include those listed under Sodium Valproate.