Methyldopa Tablets

General Notices

Action and use

Alpha₂-adrenoceptor agonist; treatment of hypertension.

Definition

Methyldopa Tablets contain Methyldopa. They are coated.

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

Content of anhydrous methyldopa, C₁₀H₁₃NO₄

95.0 to 105.0% of the stated amount.

Identification

Remove the coating from a suitable number of tablets by washing with chloroform. To a quantity of the powdered tablet cores containing the equivalent of 5 g of anhydrous methyldopa add 35 mL of a mixture of equal volumes of chloroform and methanol and shake for 3 minutes. Centrifuge and discard the supernatant liquid. Repeat the operation with a further 35 mL of a mixture of equal volumes of chloroform and methanol. Dry the residue in a current of nitrogen, add 20 mL of methanol and 15 mL of 2m hydrochloric acid, shake for 2 minutes and filter. Adjust the pH of the filtrate to 4.9 with 5m ammonia, allow to stand for several hours at 2° to 8° and filter. Wash the precipitate with 15 mL of water and dry it at 50° at a pressure not exceeding 0.7 kPa for 3 hours. Reserve a portion of the residue for the test for Optical rotation. The remainder of the residue complies with the following tests.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of methyldopa (RS 223).

B. Carry out the method for thin-layer chromatography, Appendix III A, using microcrystalline cellulose as the coating substance and a mixture of 50 volumes of butan-1-ol, 25 volumes of glacial acetic acid and 25 volumes of water as the mobile phase. Apply separately to the plate 5 µL of each of two solutions in 1m hydrochloric acid containing (1) 1% w/v of the residue and (2) 1% w/v of methyldopa BPCRS. After removal of the plate, dry it in a current of warm air and spray with a freshly prepared mixture of equal volumes of a 10% w/v solution of iron(iii) chloride hexahydrate and a 5% w/v solution of potassium hexacyanoferrate(iii). The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

C. Add 0.1 mL of iron(iii) chloride solution R1 to 5 mL of a 0.4% w/v solution in 0.1m hydrochloric acid; a green colour is produced. To half of the solution add an excess of 5m ammonia; a purple colour is produced. To the remainder of the solution add an excess of 5m sodium hydroxide; a red colour is produced.

Optical rotation

Determine the content of C₁₀H₁₃NO₄ in the residue reserved in the test for Identification by carrying out Method I for non-aqueous titration, Appendix VIII A, using 0.2 g of the residue and crystal violet solution as indicator. Each mL of 0.1m perchloric acid VS is equivalent to 21.12 mg of C₁₀H₁₃NO₄. Dissolve a quantity of the residue containing 0.39 g of C₁₀H₁₃NO₄ in sufficient aluminium chloride solution to produce 10 mL. The optical rotation of the resulting solution at 25° is –0.98° to –1.09°, Appendix V F.

Assay

Weigh and powder 20 tablets. Dissolve a quantity of the powder containing the equivalent of 0.1 g of anhydrous methyldopa as completely as possible in sufficient 0.05m sulfuric acid to produce 100 mL and filter. To 5 mL of the filtrate add 2 mL of iron(ii) sulfate–citrate solution, 8 mL of glycine buffer solution and sufficient water to produce 100 mL. Measure the absorbance of the resulting solution at the maximum at 545 nm, Appendix II B. Repeat the procedure using 5 mL of a 0.10% w/v solution of methyldopa BPCRS in place of 5 mL of the filtrate, beginning at the words ‘add 2 mL of…’. Calculate the content of C₁₀H₁₃NO₄ using the declared content of C₁₀H₁₃NO₄ in methyldopa BPCRS.

Storage

Methyldopa Tablets should be protected from light.

Labelling

The quantity of active ingredient is expressed in terms of the equivalent amount of anhydrous methyldopa.