Amiodarone Tablets

General Notices

Action and use

Potassium channel blocker; class III antiarrhythmic.

Definition

Amiodarone Tablets contain Amiodarone Hydrochloride.

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

Content of amiodarone hydrochloride, C₂₅H₂₉I₂NO₃,HCl

95.0 to 105.0% of the stated amount.

Identification

Shake a quantity of the powdered tablets containing 0.3 g of Amiodarone Hydrochloride with 25 mL of dichloromethane, filter and evaporate the filtrate to dryness. To the residue add 2 mL of 1m sodium hydroxide and extract with 25 mL of ether. Dry the extract over anhydrous sodium sulfate, filter and evaporate to dryness. Dry the residue obtained under reduced pressure over phosphorus pentoxide and dissolve in 2.5 mL of dichloromethane. The infrared absorption spectrum of the resulting solution, Appendix II A, is concordant with the reference spectrum of amiodarone (RS 008).

Related substances

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

(1) Mix with the aid of ultrasound for 15 minutes a quantity of the powdered tablets containing 50 mg of Amiodarone Hydrochloride with 50 mL of methanol, allow to cool and filter through a 0.45-µm PTFE filter. Dilute 1 volume of the solution to 2 volumes with a mixture of equal volumes of acetonitrile and water.

(2) Dilute 1 volume of solution (1) to 50 volumes and further dilute 1 volume of the resulting solution to 10 volumes with a mixture of equal volumes of acetonitrile and water.

(3) Dilute 1 volume of solution (2) to 4 volumes with a mixture of equal volumes of acetonitrile and water.

(4) Dissolve 10 mg each of (2-butylbenzofuran-3-yl)(4-hydroxy-3,5-diiodophenyl)methanone BPCRS (impurity D) and amiodarone impurity E EPCRS in methanol and dilute to 50 mL with the same solvent. Dilute 1 volume of the solution to 200 volumes with a mixture of equal volumes of acetonitrile and water.

chromatographic conditions

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Inertsil ODS(2) is suitable).

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

(d) Use a column temperature maintained at 30°.

(e) Use a detection wavelength of 240 nm.

(f) Inject 20 µL of each solution.

mobile phase

30 volumes of methanol, 40 volumes of acetonitrile and 30 volumes of a mixture prepared in the following manner: to 800 mL of water, add 3 mL of glacial acetic acid, adjust to pH 4.9 with dilute ammonia R1 and dilute to 1000 mL with water.

system suitability

The relative retention times with reference to amiodarone (retention time = 24 minutes) are: impurity A about 0.26; impurity D about 0.29; impurity E about 0.37; impurity B about 0.49; impurity C about 0.55; impurity G about 0.62; impurity F about 0.69.

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to impurity D and impurity E is at least 3.5.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity D is not greater than 2.5 times the area of the peak due to impurity D in the chromatogram obtained with solution (4) (0.5%);

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

the sum of the areas of all the secondary peaks is not greater than 5 times the area of the peak due to Amiodarone in the chromatogram obtained with solution (2) (1.0%).

Disregard any peak with an area less than the area of the peak due to amiodarone in the chromatogram obtained with solution (3) (0.05%).

Assay

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

(1) Mix with the aid of ultrasound for 15 minutes a quantity of the powdered tablets containing 50 mg of Amiodarone Hydrochloride with 100 mL of methanol, allow to cool and filter through a 0.45-µm PTFE filter. Dilute 1 volume of the solution to 5 volumes with a mixture of equal volumes of acetonitrile and water.

(2) Dilute 1 volume of a 0.05% w/v solution of amiodarone hydrochloride BPCRS in methanol to 5 volumes with a mixture of equal volumes of acetonitrile and water.

(3) Dissolve 10 mg each of (2-butylbenzofuran-3-yl)(4-hydroxy-3,5-diiodophenyl)methanone BPCRS and amiodarone impurity E EPCRS in methanol and dilute to 50 mL with the same solvent. Dilute 1 mL of the solution to 200 mL with a mixture of equal volumes of acetonitrile and water.

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 between the peaks due to impurity D and impurity E is at least 3.5.

determination of content

Calculate the content of C₂₅H₂₉I₂NO₃,HCl in the tablets using the declared content of C₂₅H₂₉I₂NO₃,HCl in amiodarone hydrochloride BPCRS.

Storage

Amiodarone Tablets should be protected from light.