It is generally conceded that the presence of salicylic acid in amounts more than traces is deleterious. Furthermore, the amount of salicylic acid is a good index of the purity of the acetylsalicylic acid, because the test is so delicate that, under favorable conditions, mere traces may be determined and, as a rule, the better the product, the less the amount of free salicylic acid.
The tests appearing in various pharmacopeias for salicylic acid as an impurity in acetylsalicylic acid do not give concordant results, different workers interpreting the results differently, nor are they detailed in such a manner as to yield maximum delicacy.
After experimentation, it was decided to establish a “limit” test of approximately 0.1 per cent. free salicylic acid, when carried out according to the following method:
0.1 gm. of the substance was placed in a dry colorimeter tube and 1 c.c. of alcohol,[206] previously distilled over NaOH, was added. After the acetylsalicylic acid had dissolved, 48 c.c. of water and 1 c.c. of fresh 0.1 per cent. ferric chloride (FeCl3.6H2O) solution were added. At the same time a control was run by treating 1 c.c. of a “standard” salicylate solution the same as above.[207] If within two minutes the color given by acetylsalicylic acid is not more intense than the color given by the “standard,” the presence of not more than 0.1 per cent. free salicylic acid is proved.[208]
The solutions used were prepared as follows:
Redistilled alcohol was treated with a small amount of sodium hydroxide for twenty-four hours, then again distilled.
The color standard was made by dissolving 0.116 gm. of dried sodium salicylate in water, adding 1 minim of glacial acetic acid, and making up to 1,000 c.c. Each c.c. represents 0.1 mg. of salicylic acid.[209]
The ferric chloride solution was made by diluting 1 c.c. ferric chloride (FeCl3.6H2O) test solution U. S. P. with 99 c.c. of water. The diluted solution must be freshly prepared each day.
With one exception, all of the commercial specimens examined responded satisfactorily to the above test showing less than 1 part salicylic acid in 1,000 parts acetylsalicylic acid. The individual results are given in the accompanying table.
Melting Point and Salicylic Acid Determinations