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Salol

C₁₃H₁₀O₃                                    214.22                               118-55-8

Benzoic acid, 2-hydroxy, phenyl ester.

Category  Intestinal antiseptic; antibacterial.

Phenyl Salicylate contains not less than 99.0 per cent and not more than 101.0 per cent of C₁₃H₁₀O₃.   

Description  Colourless crystals or a white microcrystalline powder; odour, faint and aromatic.

Solubility  Practically insoluble in water; freely soluble in ethanol; slightly soluble in glycerol.

Contra-indication  It is contra-indicated in patients with history of hypersensitivity reactions to phenyl salicylate.

Packaging and storage  Phenyl Salicylate shall be kept in tightly closed containers, protected from light, and stored at a temperature not exceeding 30º.

Identification

1. A. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
2. B. The infrared absorption spectrum is concordant with the spectrum obtained from Phenyl Salicylate RS (Appendix 2.1) or with the reference spectrum of Phenyl Salicylate.

Melting range  42º to 43.5º (Appendix 4.3).

Acidity  To a 5 per cent w/v solution in carbon dioxide-free water add phenol red TS. The solution is colourless and not more than 0.20 mL of 0.1 M sodium hydroxide is required to change the colour of the solution. 

Chloride  Not more than 360 ppm (Appendix 5.2). A 500-mg sample shows no more chloride than that corresponds to 0.25 mL of 0.020 M hydrochloric acid VS.

Sulfate  Not more than 0.12 per cent w/w (Appendix 5.2). A 500-mg sample shows no more sulfate than that corresponds to 0.62 mL of 0.010 M sulfuric acid VS.

Limit of phenol and free salicylic acid  Not more than 0.10 per cent w/w for phenol and for free salicylic acid. Carry out the test as described in the “Liquid Chromatography” (Appendix 3.5).

Diluent  Prepare a mixture of equal volumes of acetonitrile and a 0.03 per cent v/v solution of phosphoric acid.

Standard solution  Dissolve an accurately weighed quantity of Phenol RS and Salicylic Acid RS in Diluent to obtain a solution having a known concentration of 2 µg per mL of phenol and salicylic acid.

Test solution  Transfer about 200 mg of Phenyl Salicylate, accurately weighed, to a 100-mL volumetric flask, add sufficient Diluent, sonicate for 2 minutes, and dilute with Diluent to volume and mix.

Mobile phase

Mobile phase A  Prepare a 0.03 per cent v/v solution of phosphoric acid.

Mobile phase B  Acetonitrile.

The step gradient of mobile phases is as follows.

Chromatographic System

Detector  Ultraviolet light (275 nm for Phenol and 235 nm for Salicylic acid).

Column  A stainless steel column (75 mm × 4.6 mm), packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3.5 µm).

Temperature  

   Column  About 35º.

Flow rate  2.0 mL per minute.

System suitability

Sample  Standard solution. 

Suitability requirements 

Symmetry factor  Not more than 2.0 for the phenol and salicylic acid peaks.

Resolution  Not less than 2.0 between the phenol and salicylic acid peaks.

Relative standard deviation  Not more than 2.0 per cent for the phenol and salicylic acid peaks.

COLUMN EFFICIENCY  Not less than 2,000 theoretical plates for the phenol and salicylic acid peaks.

Procedure  Separately inject equal volumes (about 20 µL) of Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Identify the peaks due to phenol and salicylic acid in the test solution, using the retention times of phenol and salicylic acid in the standard solution.

Calculation  Calculate the contents of C₆H₆O and C₇H₆O₃ in the portion of the Phenyl Salicylate taken, using the declared contents of C₆H₆O in Phenol RS and C₇H₆O₃ in Salicylic Acid RS.

Assay  Carry out the determination as described in the “Liquid Chromatography” (Appendix 3.5).

Diluent  Acetonitrile and water (75:25).

Standard preparation  Dissolve an accurately weighed quantity of Phenyl Salicylate RS, in Diluent to obtain a solution having a known concentration of 600 µg per mL.

Assay preparation  Transfer about 60 mg of Phenyl Salicylate, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.

Mobile phase  Acetonitrile and water (50:50).

Chromatographic system

Detector  Ultraviolet light (275 nm).

Column  A stainless steel column (150 mm × 4.6 mm), packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (5 µm).

Temperature  

   Column  About 35º.

Flow rate  2.0 mL per minute.

System suitability

          Sample  Standard preparation. 

Suitability requirements

          Symmetry factor  Not more than 2.0.

          Relative standard deviation  Not more than 2.0 per cent.

          COLUMN EFFICIENCY  Not less than 2,000 theoretical plates.

Procedure  Separately inject equal volumes (about 10 L) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.

Calculation  Calculate the content of C₁₃H₁₀O₃ in the portion of the Phenyl Salicylate taken, using the declared content of C₁₃H₁₀O₃ in Phenyl Salicylate RS.