B. To 0.2 g add 4 mL of dilute sodium hydroxide solution R and boil for 3 min. Cool and add 5 mL of dilute sulfuric acid R. A crystalline precipitate is formed. Filter, wash the precipitate and dry at 100-105 °C. The melting point (2.2.14) is 156 °C to 161 °C.

C. In a test tube mix 0.1 g with 0.5 g of calcium hydroxide R. Heat the mixture and expose to the fumes produced a piece of filter paper impregnated with 0.05 mL of nitrobenzaldehyde solution R. A greenish-blue or greenish-yellow colour develops on the paper. Moisten the paper with dilute hydrochloric acid R. The colour becomes blue.

D. Dissolve with heating about 20 mg of the precipitate obtained in identification test B in 10 mL of water R and cool. The solution gives reaction (a) of salicylates (2.3.1).

TESTS

Appearance of solution

The solution is clear (2.2.1) and colourless (2.2.2, Method II).

Dissolve 1.0 g in 9 mL of ethanol (96 per cent) R.

Related substances

Liquid chromatography (2.2.29). Prepare the solutions immediately before use.

Test solution Dissolve 0.100 g of the substance to be examined in acetonitrile for chromatography R and dilute to 10.0 mL with the same solvent.

Reference solution (a) Dissolve 50.0 mg of salicylic acid R (impurity C) in the mobile phase and dilute to 50.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 100.0 mL with the mobile phase.

Reference solution (b) Dissolve 10 mg of salicylic acid R (impurity C) in the mobile phase and dilute to 10.0 mL with the mobile phase. To 1.0 mL of this solution add 0.2 mL of the test solution and dilute to 100.0 mL with the mobile phase.

Column:

— size: l = 0.25 m, Ø = 4.6 mm;

— stationary phase: octadecylsilyl silica gel for chromatography R (5 µm).

Mobile phase phosphoric acid R, acetonitrile for chromatography R, water R (2:400:600 V/V/V).

Flow rate 1 mL/min.

Detection Spectrophotometer at 237 nm.

Injection 10 µL.

Run time 7 times the retention time of acetylsalicylic acid.

Identification of impurities Use the chromatogram obtained with reference solution (a) to identify the peak due to impurity C.

Relative retention With reference to acetylsalicylic acid (retention time = about 5 min): impurity A = about 0.7; impurity B = about 0.8; impurity C = about 1.3; impurity D = about 2.3; impurity E = about 3.2; impurity F = about 6.0.

System suitability Reference solution (b):

— resolution: minimum 6.0 between the peaks due to acetylsalicylic acid and impurity C.

Limits:

— impurities A, B, C, D, E, F: for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 per cent);

— unspecified impurities: for each impurity, not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent);

— total: not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.25 per cent);

— disregard limit: 0.3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.03 per cent).

Heavy metals (2.4.8)

Maximum 20 ppm.

Dissolve 1.0 g in 12 mL of acetone R and dilute to 20 mL with water R. 12 mL of the solution complies with test B. Prepare the reference solution using lead standard solution (1 ppm Pb) obtained by diluting lead standard solution (100 ppm Pb) R with a mixture of 6 volumes of water R and 9 volumes of acetone R.

Loss on drying (2.2.32)

Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo.

Sulfated ash (2.4.14)

Maximum 0.1 per cent, determined on 1.0 g.

ASSAY

In a flask with a ground-glass stopper, dissolve 1.000 g in 10 mL of ethanol (96 per cent) R. Add 50.0 mL of 0.5 M sodium hydroxide. Close the flask and allow to stand for 1 h. Using 0.2 mL of phenolphthalein solution R as indicator, titrate with 0.5 M hydrochloric acid. Carry out a blank titration.

1 mL of 0.5 M sodium hydroxide is equivalent to 45.04 mg of C₉H₈O₄.

STORAGE

In an airtight container.

IMPURITIES

Specified impurities A, B, C, D, E, F.

bp2012_v1_07_medicinal_and_pharmaceutical_substances_2 acetylsalicylicacid_2_2012_70_cs.png

A. 4-hydroxybenzoic acid,

bp2012_v1_07_medicinal_and_pharmaceutical_substances_2 acetylsalicylicacid_3_2012_70_cs.png

B. 4-hydroxybenzene-1,3-dicarboxylic acid (4-hydroxyisophthalic acid),

bp2012_v1_07_medicinal_and_pharmaceutical_substances_2 acetylsalicylicacid_4_2012_70_cs.png

C. 2-hydroxybenzenecarboxylic acid (salicylic acid),

bp2012_v1_07_medicinal_and_pharmaceutical_substances_2 acetylsalicylicacid_5_2012_70_cs.png

D. 2-[[2-(acetyloxy)benzoyl]oxy]benzoic acid (acetylsalicylsalicylic acid),

bp2012_v1_07_medicinal_and_pharmaceutical_substances_2 acetylsalicylicacid_6_2012_70_cs.png

E. 2-[(2-hydroxybenzoyl)oxy]benzoic acid (salicylsalicylic acid),

bp2012_v1_07_medicinal_and_pharmaceutical_substances_2 acetylsalicylicacid_7_2012_70_cs.png

F. 2-(acetyloxy)benzoic anhydride (acetylsalicylic anhydride).

Ph Eur