Co-tenidone Tablets

General Notices

Atenolol and Chlortalidone Tablets

Action and use

Beta-adrenoreceptor antagonist + thiazide like diuretic.

Definition

Co-tenidone Tablets contain Atenolol and Chlortalidone in the proportions, by weight, 4 parts to 1 part.

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

Content of atenolol, C14H22N2O3

95.0 to 105.0% of the stated amount.

Content of chlortalidone, C14H11ClN2O4S

92.5 to 107.5% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Remove any film coating from the tablets, powder and shake a quantity of the powdered tablets containing 0.1 g of atenolol with 10 mL of methanol for 15 minutes and filter.
(2) 1.0% w/v of atenolol BPCRS in methanol.
(3) 0.25% w/v of chlortalidone BPCRS in methanol.
chromatographic conditions
(a) Use as the coating silica gel GF254.
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm).
mobile phase

30 volumes of 18m ammonia and 150 volumes of butan-1-ol.

confirmation

In the chromatogram obtained with solution (1) the two principal spots correspond in position, size and intensity to those of the principal spots in the chromatograms obtained with solutions (2) and (3).

B. In the Assay, the retention times of the two principal peaks in the chromatogram obtained with solution (1) correspond to those of the principal peaks in the chromatograms obtained with solutions (2) and (3).

Related substances

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

(1) Remove any film coating from the tablets, powder and shake a quantity of the powder containing 0.1 g of atenolol (and 0.025 g of chlortalidone) with 25 mL of the mobile phase for 30 minutes with the aid of ultrasound. Filter through a suitable filter (Whatman No l is suitable) and use the filtrate.
(2) Dilute 1 volume of solution (1) to 200 volumes with the mobile phase.
(3) Dissolve 50 mg of atenolol impurity standard BPCRS in 0.1 mL of dimethyl sulfoxide, with the aid of gentle heat, and dilute to 100 mL with the mobile phase.
(4) 0.002% w/v of 2-(4-chloro-3-sulfamoylbenzoyl)benzoic acid BPCRS in the mobile phase.
chromatographic conditions
(a) Use 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) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use ambient column temperature.
(e) Use a detection wavelength of 226 nm.
(f) Inject 20 µL of each solution.
mobile phase

20 volumes of tetrahydrofuran, 180 volumes of methanol and 800 volumes of 0.025m potassium dihydrogen orthophosphate containing 1.0 g of sodium octanesulfonate and 0.4 g of tetrabutylammonium hydrogen sulfate per litre and adjusted to pH 3.0 with orthophosphoric acid.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) closely resembles the reference chromatogram supplied with atenolol impurity standard BPCRS and the peaks corresponding to tertiary amine, which is usually a doublet, and bis ether are clearly separated. If necessary, adjust the concentration of sodium octanesulfonate in the mobile phase; increasing the concentration increases the retention time of the tertiary amine.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 2-(4-chloro-3-sulfamoyl-benzoyl)benzoic acid is not greater than the area of the peak in the chromatogram obtained with solution (4) (2%, with reference to the content of chlortalidone);

the area of any peak corresponding to blocker acid is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%, with reference to the content of atenolol);

the area of any peak corresponding to either tertiary amine or bis ether is not greater than half of the area of the principal peak in the chromatogram obtained with solution (2) (0.25%, with reference to the content of atenolol).

Assay

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

(1) Extract a quantity of the powder containing 0.1 g of atenolol with 70 mL of the mobile phase by shaking with the aid of ultrasound for 30 minutes, allow to cool, add sufficient of the mobile phase to produce 100 mL, filter and use the filtrate.
(2) 0.1% w/v of atenolol BPCRS in the mobile phase.
(3) 0.025% w/v of chlortalidone BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use ambient column temperature.
(e) Use a detection wavelength of 275 nm.
(f) Inject 20 µL of each solution.
mobile phase

10 volumes of sulfuric acid (10%), 50 volumes of propan-2-ol, 200 volumes of acetonitrile and 740 volumes of water containing 0.5 g per litre of sodium octanesulfonate and adjusted to pH 3.0 with 2m sodium hydroxide.

determination of content

Calculate the content of C14H22N2O3 and of C14H11ClN2O4S using the declared contents of C14H22N2O3 and of C14H11ClN2O4S in atenolol BPCRS and in chlortalidone BPCRS, respectively.

When atenolol and chlorthalidone tablets are prescribed or demanded, Co-tenidone Tablets shall be dispensed or supplied.