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Salicylic Acid
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C7H6O3 138.12

Benzoic acid, 2-hydroxy-.
Salicylic acid [69-72-7].
» Salicylic Acid contains not less than 99.5 percent and not more than 101.0 percent of C7H6O3, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification— It meets the requirements of the tests for Salicylate 191.
Melting range 741: between 158 and 161.
Loss on drying 731 Dry it over silica gel for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.05%.
Chloride 221 Heat 1.5 g with 75 mL of water until the acid is dissolved, cool, add water to restore the original volume, and filter: a 25-mL portion of the filtrate shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (0.014%).
Sulfate— Dissolve 12.0 g in 37 mL of acetone, and add 3 mL of water. Titrate potentiometrically with 0.02 M lead perchlorate, prepared by dissolving 9.20 g of lead perchlorate in water to make 1000 mL of solution, using a pH meter capable of a minimum reproducibility of ±0.1 mV (see pH 791) equipped with an electrode system consisting of a lead-specific electrode and a silver-silver chloride reference glass-sleeved electrode containing a solution of tetraethylammonium perchlorate in glacial acetic acid (1 in 44): not more than 1.25 mL of 0.02 M lead perchlorate is consumed (0.02%).
Heavy metals— Dissolve 1 g in 25 mL of acetone, and add 2 mL of water. Add 1.2 mL of thioacetamide-glycerin base TS and 2 mL of pH 3.5 Acetate Buffer, and allow to stand for 5 minutes: any color produced is not darker than that of a control made with 25 mL of acetone and 2 mL of Standard Lead Solution (see Heavy Metals 231) and treated in the same manner. The limit is 20 µg per g.
Related compounds—
Mobile phase— Prepare a mixture of water, methanol, and glacial acetic acid (60:40:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Prepare a mixture of methanol, water, and glacial acetic acid (70:30:4).
Reference solutions— Prepare a solution in Diluent containing about 0.05 mg of 4-hydroxybenzoic acid and 0.025 mg of 4-hydroxyisophthalic acid per mL, and a second solution in Diluent containing about 0.05 mg of 4-hydroxybenzoic acid and 0.01 mg of phenol per mL.
Standard solution— Dissolve accurately weighed quantities of 4-hydroxybenzoic acid, 4-hydroxyisophthalic acid, phenol, and the Salicylic Acid under test in Diluent to obtain a solution having known concentrations of about 0.05 mg per mL, 0.025 mg per mL, 0.01 mg per mL, and 50 mg per mL, respectively.
Test solution— Prepare a solution of Salicylic Acid in Diluent containing 50 mg per mL. Sonicate until completely dissolved.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 270-nm detector and a 4.6-mm × 10-cm column containing 5-µm packing L1. The flow rate is about 0.5 mL per minute. Chromatograph the Reference solutions, record the chromatograms, and note the retention times of the peaks. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.35, 0.45, 0.5, and 1.0 for 4-hydroxybenzoic acid, 4-hydroxyisophthalic acid, phenol, and salicylic acid, respectively, and the peaks are all baseline-resolved from each other. Changes in the composition of the Mobile phase made to optimize resolution may change the elution order of impurities. Use the chromatograms obtained from the Reference solutions to determine the elution order of the specified impurities.
Procedure— Separately inject equal volumes (about 2 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the percentage of each relevant related compound taken by the formula:
2Ci [ri / (rSi ri)],
in which Ci is the concentration, in mg per mL, of the relevant related compound in the Standard solution; and ri and rSi are the peak responses for the relevant related compound obtained from the Test solution and the Standard solution, respectively: not more than 0.1% of 4-hydroxybenzoic acid, 0.05% of 4-hydroxyisophthalic acid, and 0.02% of phenol is found. Calculate the percentage of any other impurity, other than the solvent peak, observed in the chromatogram of the Test solution by the same formula, except to use the concentration of 4-hydroxyisophthalic acid in the Standard solution as Ci; the response of the peak of 4-hydroxyisophthalic acid in the chromatogram obtained from the Standard solution as rSi; and the response of any other impurity as ri: not more than 0.05% of any other impurity is found; and the sum of all of the related compounds and other impurities found is not more than 0.2%.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 500 mg of Salicylic Acid, accurately weighed, in 25 mL of diluted alcohol that previously has been neutralized with 0.1 N sodium hydroxide, add phenolphthalein TS, and titrate with 0.1 N sodium hydroxide VS. Each mL of 0.1 N sodium hydroxide is equivalent to 13.81 mg of C7H6O3.
Auxiliary Information— Staff Liaison : Feiwen Mao, M.S., Senior Scientific Associate
Expert Committee : (MDOOD05) Monograph Development-Ophthalmics Oncologics and Dermatologicals
USP29–NF24 Page 1940
Phone Number : 1-301-816-8320