Atenolol Tablets

General Notices

Action and use

Beta-adrenoceptor antagonist.

Definition

Atenolol Tablets contain Atenolol.

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

Content of atenolol, C14H22N2O3

92.5 to 107.5% of the stated amount.

Identification

A. Heat a quantity of the powdered tablets containing 0.1 g of Atenolol with 15 mL of methanol to 50°, shake for 5 minutes, filter (Whatman No. 42 paper is suitable) and evaporate the filtrate to dryness on a water bath. Warm the residue with 10 mL of 0.1m hydrochloric acid, shake and filter. Add to the filtrate sufficient 1m sodium hydroxide to make it alkaline, extract with 10 mL of chloroform, dry by shaking with anhydrous sodium sulfate, filter, evaporate the filtrate to dryness on a water bath and dry the residue at 105° for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of atenolol (RS 015).
B. The light absorption, Appendix II B, in the range 230 to 350 nm of the solution obtained in the Assay exhibits maxima at 275 nm and 282 nm.

Tests

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 25 mg of Atenolol with 25 mL of the mobile phase, mix with the aid of ultrasound for 20 minutes, filter (Whatman GF/C filter paper is suitable) and use the filtrate. For solution (2) dilute 1 volume of solution (1) to 200 volumes with the mobile phase. For solution (3) dissolve 10 mg of atenolol impurity standard BPCRS in 0.1 mL of dimethyl sulfoxide, with the aid of gentle heat, add 10 mL of the mobile phase and mix.

The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 2 is suitable), (b) as the mobile phase with a flow rate of 1 mL per minute a mixture prepared as described below and (c) a detection wavelength of 226 nm. For the mobile phase dissolve 0.8 g of sodium octanesulfonate and 0.4 g of tetrabutylammonium hydrogen sulfate in 1 litre of a mixture of 20 volumes of tetrahydrofuran, 180 volumes of methanol and 800 volumes of a 0.34% w/v solution of potassium dihydrogen orthophosphate; adjust the pH to 3.0 with orthophosphoric acid. Inject 20 µL of each solution.

The test is not valid unless the chromatogram obtained with solution (3) resembles the reference chromatogram provided with atenolol impurity standard BPCRS in that the peak due to bis ether precedes, and is separated from, that due to tertiary amine, which is normally a doublet. If necessary, adjust the concentration of sodium octanesulfonate in the mobile phase; increasing the concentration increases the retention time of the tertiary amine.

In the chromatogram obtained with solution (1) the area of any peak corresponding to blocker acid is not greater than the area of the peak in the chromatogram obtained with solution (2) (0.5%) and the area of any peak corresponding to either tertiary amine or bis ether is not greater than half of the area of the peak in the chromatogram obtained with solution (2) (0.25%).

Assay

Powder 20 tablets. Transfer the powder to a 500 mL flask using 300 mL of methanol, heat the resulting suspension to 60° and shake for 15 minutes. Cool, dilute to 500 mL with methanol, filter through a fine glass micro-fibre filter paper (Whatman GF/C is suitable) and dilute a suitable volume of the filtrate with sufficient methanol to produce a solution containing 0.01% w/v of Atenolol. Measure the absorbance of the resulting solution at the maximum at 275 nm, Appendix II B. Calculate the content of C14H22N2O3 taking 53.7 as the value of A(1%, 1 cm) at the maximum at 275 nm.