Verapamil Tablets

General Notices

Action and use

Calcium channel blocker.

Definition

Verapamil Tablets contain Verapamil Hydrochloride. They are coated.

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

Content of verapamil hydrochloride, C₂₇H₃₈N₂O₄,HCl

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 0.1 g of Verapamil Hydrochloride with 25 mL of 0.1m hydrochloric acid, filter, extract the filtrate with 25 mL of ether, discard the extract and make the aqueous solution just alkaline with 2m potassium carbonate sesquihydrate. Extract with 25 mL of ether, filter the ether layer through anhydrous sodium sulfate and evaporate to dryness. The infrared absorption spectrum of a thin film of the oily residue, Appendix II A, is concordant with the reference spectrum of verapamil (RS 359).

B. Shake a quantity of the powdered tablets containing 0.1 g of Verapamil Hydrochloride with 10 mL of dichloromethane, filter, evaporate the filtrate to dryness and dissolve the residue in 10 mL of water. To 2 mL of the resulting solution add 0.2 mL of a 5% w/v solution of mercury(ii) chloride. A white precipitate is produced.

C. To 2 mL of the solution obtained in test B add 0.5 mL of 3m sulfuric acid and 0.2 mL of dilute potassium permanganate solution. A violet precipitate is produced which quickly dissolves to produce a very pale yellow solution.

Tests

Related substances

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

(1) Shake a quantity of the powdered tablets containing 0.24 g of Verapamil Hydrochloride with 90 mL of mobile phase, add sufficient of the mobile phase to produce 100 mL, centrifuge and use the supernatant liquid.

(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase and further dilute 1 volume of the resulting solution to 10 volumes with the same solvent.

(3) 0.005% w/v of verapamil hydrochloride BPCRS and 0.005% w/v of verapamil impurity I EPCRS in the mobile phase.

chromatographic conditions

(a) Use a stainless steel column (12.5 cm × 4 mm) packed with octadecylsilyl silica gel for chromatography (3 µm) (Hypersil ODS is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 278 nm.

(f) Inject 10 µL of each solution.

(g) Allow the chromatography to proceed for 4 times the retention time of verapamil.

mobile phase

1 volume of n-heptylamine, 4.7 volumes of glacial acetic acid, 58 volumes of acetonitrile and 137 volumes of 0.01m sodium acetate.

system suitability

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

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%);

the sum of the areas of any such peaks is not greater than 3 times the principal peak in the chromatogram obtained with solution (2) (0.3%).

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

Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.1 g of Verapamil Hydrochloride with 150 mL of 0.1m hydrochloric acid for 10 minutes, add sufficient 0.1m hydrochloric acid to produce 200 mL and filter. Dilute 10 mL of the filtrate to 100 mL with water and measure the absorbance of the resulting solution at the maximum at 278 nm, Appendix II B. Calculate the content of C₂₇H₃₈N₂O₄,HCl taking 118 as the value of A(1%, 1 cm) at the maximum at 278 nm.