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Category Antiprotozoal (antimalarial).

Artesunate contains not less than 99.0 per cent and not more than 101.0 per cent of C₁₉H₂₈O₈, calculated on the anhydrous basis.

Description Fine, white crystalline powder.

Solubility Very slightly soluble in water; very soluble in dichloromethane; freely soluble in acetone and in ethanol.

Warning
          1. It should not be used at all for prophylaxis of malaria.
          2. It should not be used during the first trimester of pregnancy. Risk-benefit should be considered if it is to be used in pregnant women.
          3. It may cause mild gastro-intestinal disturbances, dizziness, tinnitus, neutropenia, elevated liver enzyme values, electrocardiogram abnormalities including prolongation of the QT interval, acute cerebellar dysfunction, bone marrow depression or reticulocytopenia.
          4. It should be used with caution in patients with cardiac, hepatic, renal and gastro-intestinal diseases.

Packaging and storage Artesunate shall be kept in well-closed containers, protected from light, and stored at a temperature not exceeding 25º.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Artesunate RS (Appendix 2.1) or with the reference spectrum of Artesunate.
          B. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel GF254 as the coating substance and a mixture of 5 volumes of ethyl acetate and 95 volumes of toluene as the mobile phase. Apply separately to the plate, 2 μl of the following two solutions in toluene containing (A) 100 μg of the test substance per ml, and (B) 100 μg of Artesunate RS per ml. After removal of the plate, allow it to dry in air, spray with anisaldehyde TS, heat the plate to 120º for 5 minutes and examine under ultraviolet light (254 nm): the principal spot obtained from solution (A) corresponds in position, appearance and intensity to that obtained from solution (B).
          C. Dissolve 100 mg of the test substance in 40 ml of absolute ethanol, shake and filter. To half of the filtrate (keep the remaining filtrate for test D) add about 0.5 ml of hydroxylamine in ethanol TS and 5 drops of sodium hydroxide TS. Heat the mixture in a water-bath to boiling, cool, and add 2 to 3 drops of dilute hydrochloric acid and 1 drop of iron(III) chloride TS: a light red-violet colour is produced.
          D. Evaporate the remaining filtrate from Test C on a water-bath to a volume of about 5 ml. Place a few drops of the mixture on a white porcelain dish, add one drop of vanillin-sulfuric acid TS1, and allow to stand for 30 minutes: a red colour is produced.

Melting range 132º to 135º (Appendix 4.3).

pH 3.5 to 4.5, in a 1 per cent w/w suspension (Appendix 4.11).

Specific rotation +2.5º to +3.5º, determined in a 1.0 per cent w/v solution in dichloromethane (Appendix 4.8).

Water Not more than 0.5 per cent w/w (Karl Fischer Method, Appendix 4.12).

Heavy metals Not more than 20 ppm (Method II, Appendix 5.2). Use 1.0 g; for the Standard Preparation, use lead standard solution (1 ppm Pb).

Sulfated ash Not more than 0.1 per cent w/w (Appendix 5.3).

Related substances Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel G as the coating substance.
          Reference solution 1 Prepare a 0.005 per cent w/v solution of the test substance in dichloromethane.
          Reference solution 2 Prepare a 0.0025 per cent w/v solution of the test substance in dichloromethane.
          Test solution Prepare a 0.5 per cent w/v solution of the test substance in dichloromethane.
          Mobile phase Prepare a mixture of 48 volumes of petroleum ether (boiling range, 30º to 40º), 36 volumes of ethyl acetate and 1 volume of glacial acetic acid.
          Procedure Apply separately to the plate, 10 μl of each of the solutions. After removal of the plate, allow it to dry in air, spray with vanillin-sulfuric acid TS1, and examine the chromatogram in daylight. Any spot
obtained from Test solution, other than the principal spot, is not more intense than that obtained from Reference solution 1 (1.0 per cent). Furthermore, not more than one such spot is more intense than that obtained from Reference solution 2 (0.5 per cent).

Assay Dissolve about 250 mg of Artesunate, accurately weighed, in 25 ml of neutralized ethanol and titrate with 0.05 M sodium hydroxide VS, using dilute phenolphthalein TS as indicator. Perform a blank determination, and make any necessary correction. Each ml of 0.05 M sodium hydroxide is equivalent to 19.22 mg of C₁₉H₂₈O₈.