Betahistine Dihydrochloride Tablets

General Notices

Action and use

Histamine H1 receptor antagonist; antihistamine.

Definition

Betahistine Dihydrochloride Tablets contain Betahistine Dihydrochloride.

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

Content of betahistine dihydrochloride, C8H12N2,2HCl

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 5 mg of Betahistine Dihydrochloride with 100 mL of water and filter. The light absorption, Appendix II B, in the range 230 to 350 nm exhibits a maximum at about 260 nm, a less well-defined maximum at about 267 nm and a shoulder at about 256 nm.
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Tests

Related substances

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

(1) Add 50 mL of the mobile phase to a quantity of the powdered tablets containing 32 mg of Betahistine Dihydrochloride, shake for 10 minutes, add sufficient mobile phase to produce 100 mL, mix, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 500 volumes with the mobile phase.
(3) 0.00064% w/v of N-methyl-2-(pyridin-2-yl)-N-[2-(pyridine-2-yl)ethyl]ethanamine trihydrochloride BPCRS in the mobile phase.
(4) 0.000032% w/v of 2-vinylpyridine in acetonitrile.
(5) 0.00064% w/v each of N-methyl-2-(pyridin-2-yl)-N-[2-(pyridine-2-yl)ethyl]ethanamine trihydrochloride BPCRS and betahistine dihydrochloride BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Zorbax XDB Eclipse is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use a column temperature of 30°.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for four times the retention time of betahistine (retention time of betahistine, about 5 minutes).
mobile phase

Dissolve 0.4 g of hexylamine in 600 mL of a solution containing 0.46% w/v of sodium dihydrogen orthophosphate monohydrate and 0.27% w/v of sodium dodecyl sulfate, add 400 mL of acetonitrile, mix and adjust the pH to 3.5 using orthophosphoric acid.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution factor between the two principal peaks is at least 3.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to N-methyl-bis[β-(2-pyridyl)ethyl]amine is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (2%);

the area of any peak corresponding to 2-vinylpyridine is not greater than twice the area of the principal peak in the chromatogram obtained with solution (4) (0.2%);

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

the sum of the areas of the peaks corresponding to N-methyl-bis[β-(2-pyridyl)ethyl]amine, 2-vinylpyridine and any other secondary peaks is not greater than 10 times the area of the principal peak in the chromatogram obtained with solution (2) (2%).

Disregard any peak with an area less than 0.05% of that of the principal peak in the chromatogram obtained with solution (1) (0.05%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add 50 mL of the mobile phase to a quantity of the powdered tablets containing 32 mg of Betahistine Dihydrochloride, shake for 10 minutes, add sufficient mobile phase to produce 100 mL, mix, centrifuge and use the supernatant liquid.
(2) 0.032% w/v of betahistine dihydrochloride BPCRS in the mobile phase.
(3) 0.00064% w/v each of N-methyl-2-(pyridin-2-yl)-N-[2-(pyridine-2-yl)ethyl]ethanamine trihydrochloride BPCRS and betahistine dihydrochloride BPCRS in the mobile phase.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 3.0.

determination of content

Calculate the content of C8H12N2,2HCl in the tablets using the declared content of C8H12N2,2HCl in betahistine dihydrochloride BPCRS.

Storage

Betahistine Dihydrochloride Tablets should be protected from light and moisture.

IMPURITIES

1. 2-ethenylpyridine (2-vinylpyridine),
2. 2-(pyridin-2-yl)ethanol,
3. N-methyl-2-(pyridin-2-yl)-N-[2-(pyridin-2-yl)ethyl]ethanamine.